Kim Butts Pauly

All Publications

• Remote, brain region-specific control of choice behavior with ultrasonic waves SCIENCE ADVANCES Kubanek, J., Brown, J., Ye, P., Pauly, K., Moore, T., Newsome, W. 2020; 6 (21)

  View details for DOI 10.1126/sciadv.aaz4193

  View details for Web of Science ID 000537235300018

• Histologic safety of transcranial focused ultrasound neuromodulation and magnetic resonance acoustic radiation force imaging in rhesus macaques and sheep. Brain stimulation Gaur, P., Casey, K. M., Kubanek, J., Li, N., Mohammadjavadi, M., Saenz, Y., Glover, G. H., Bouley, D. M., Pauly, K. B. 2020; 13 (3): 804–14

  Abstract

  BACKGROUND: Neuromodulation by transcranial focused ultrasound (FUS) offers the potential to non-invasively treat specific brain regions, with treatment location verified by magnetic resonance acoustic radiation force imaging (MR-ARFI).OBJECTIVE: To investigate the safety of these methods prior to widespread clinical use, we report histologic findings in two large animal models following FUS neuromodulation and MR-ARFI.METHODS: Two rhesus macaques and thirteen Dorset sheep were studied. FUS neuromodulation was targeted to the primary visual cortex in rhesus macaques and to subcortical locations, verified by MR-ARFI, in eleven sheep. Both rhesus macaques and five sheep received a single FUS session, whereas six sheep received repeated sessions three to six days apart. The remaining two control sheep did not receive ultrasound but otherwise underwent the same anesthetic and MRI procedures as the eleven experimental sheep. Hematoxylin and eosin-stained sections of brain tissue (harvested zero to eleven days following FUS) were evaluated for tissue damage at FUS and control locations as well as tissue within the path of the FUS beam. TUNEL staining was used to evaluate for the presence of apoptosis in sheep receiving high dose FUS.RESULTS: No FUS-related pre-mortem histologic findings were observed in the rhesus macaques or in any of the examined sheep. Extravascular red blood cells (RBCs) were present within the meninges of all sheep, regardless of treatment group. Similarly, small aggregates of perivascular RBCs were rarely noted in non-target regions of neural parenchyma of FUS-treated (8/11) and untreated (2/2) sheep. However, no concurrent histologic abnormalities were observed, consistent with RBC extravasation occurring as post-mortem artifact following brain extraction. Sheep within the high dose FUS group were TUNEL-negative at the targeted site of FUS.CONCLUSIONS: The absence of FUS-related histologic findings suggests that the neuromodulation and MR-ARFI protocols evaluated do not cause tissue damage.

  View details for DOI 10.1016/j.brs.2020.02.017

  View details for PubMedID 32289711

• Elimination of peripheral auditory pathway activation does not affect motor responses from ultrasound neuromodulation. Brain stimulation Mohammadjavadi, M., Ye, P. P., Xia, A., Brown, J., Popelka, G., Pauly, K. B. 2019

  Abstract

  BACKGROUND: Recent studies in a variety of animal models including rodents, monkeys, and humans suggest that transcranial focused ultrasound (tFUS) has considerable promise for non-invasively modulating neural activity with the ability to target deep brain structures. However, concerns have been raised that motor responses evoked by tFUS may be due to indirect activation of the auditory pathway rather than direct activation of motor circuits.OBJECTIVE: In this study, we sought to examine the involvement of peripheral auditory system activation from tFUS stimulation applied to elicit motor responses. The purpose was to determine to what extent ultrasound induced auditory artifact could be a factor in ultrasound motor neuromodulation.METHODS: In this study, tFUS-induced electromyography (EMG) signals were recorded and analyzed in wild-type (WT) normal hearing mice and two strains of genetically deaf mice to examine the involvement of the peripheral auditory system in tFUS-stimulated motor responses. In addition, auditory brainstem responses (ABRs) were measured to elucidate the effect of the tFUS stimulus envelope on auditory and motor responses. We also varied the tFUS stimulation duration to measure its effect on motor response duration.RESULTS: We show, first, that the sharp edges in a tFUS rectangular envelope stimulus activate the peripheral afferent auditory pathway and, second, that smoothing these edges eliminates the auditory responses without affecting the motor responses in normal hearing WT mice. We further show that by eliminating peripheral auditory activity using two different strains of deaf knockout mice, motor responses are the same as in normal hearing WT mice. Finally, we demonstrate a high correlation between tFUS pulse duration and EMG response duration.CONCLUSION: These results support the concept that tFUS-evoked motor responses are not a result of stimulation of the peripheral auditory system.

  View details for PubMedID 30880027

• Radiation force as a physical mechanism for ultrasonic neurostimulation of the ex vivo retina. The Journal of neuroscience : the official journal of the Society for Neuroscience Menz, M. D., Ye, P. n., Firouzi, K. n., Nikoozadeh, A. n., Butts Pauly, K. n., Khuri-Yakub, P. n., Baccus, S. A. 2019

  Abstract

  Focused ultrasound has been shown to be effective at stimulating neurons in many animal models, both in vivo and ex vivo. Ultrasonic neuromodulation is the only non-invasive method of stimulation that could reach deep in the brain with high spatial-temporal resolution, and thus has potential for use in clinical applications and basic studies of the nervous system. Understanding the physical mechanism by which energy in a high acoustic frequency wave is delivered to stimulate neurons will be important to optimize this technology. We imaged the isolated salamander retina of either sex during ultrasonic stimuli that drive ganglion cell activity and observed micron scale displacements, consistent with radiation force, the nonlinear delivery of momentum by a propagating wave. We recorded ganglion cell spiking activity and changed the acoustic carrier frequency across a broad range (0.5 - 43 MHz), finding that increased stimulation occurs at higher acoustic frequencies, ruling out cavitation as an alternative possible mechanism. A quantitative radiation force model can explain retinal responses and could potentially explain previous in vivo results in the mouse, suggesting a new hypothesis to be tested in vivo. Finally, we found that neural activity was strongly modulated by the distance between the transducer and the electrode array showing the influence of standing waves on the response. We conclude that radiation force is the dominant physical mechanism underlying ultrasonic neurostimulation in the ex vivo retina and propose that the control of standing waves is a new potential method to modulate these effects.SIGNIFICANCE STATEMENTUltrasonic neurostimulation is a promising noninvasive technology that has potential for both basic research and clinical applications. The mechanisms of ultrasonic neurostimulation are unknown, making it difficult to optimize in any given application. We studied the physical mechanism by which ultrasound is converted into an effective energy form to cause neurostimulation in the retina and find that ultrasound acts through radiation force leading to a mechanical displacement of tissue. We further show that standing waves have a strong modulatory effect on activity. Our quantitative model by which ultrasound generates radiation force and leads to neural activity will be important in optimizing ultrasonic neurostimulation across a wide range of applications.

  View details for DOI 10.1523/JNEUROSCI.2394-18.2019

  View details for PubMedID 31196935

• A rapid beam simulation framework for transcranial focused ultrasound. Scientific reports Leung, S. A., Webb, T. D., Bitton, R. R., Ghanouni, P. n., Butts Pauly, K. n. 2019; 9 (1): 7965

  Abstract

  Transcranial focused ultrasound is a non-invasive therapeutic modality that can be used to treat essential tremor. Beams of energy are focused into a small spot in the thalamus, resulting in tissue heating and ablation. Here, we report on a rapid 3D numeric simulation framework that can be used to predict focal spot characteristics prior to the application of ultrasound. By comparing with magnetic resonance proton resonance frequency shift thermometry (MR thermometry) data acquired during treatments of essential tremor, we verified that our simulation framework can be used to predict focal spot position, and with patient-specific calibration, predict focal spot temperature rise. Preliminary data suggests that lateral smearing of the focal spot can be simulated. The framework may also be relevant for other therapeutic ultrasound applications such as blood brain barrier opening and neuromodulation.

  View details for DOI 10.1038/s41598-019-43775-6

  View details for PubMedID 31138821

• Measurements of the Relationship Between CT Hounsfield Units and Acoustic Velocity and How It Changes With Photon Energy and Reconstruction Method IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Webb, T. D., Leung, S. A., Rosenberg, J., Ghanouni, P., Dahl, J. J., Pelc, N. J., Pauly, K. 2018; 65 (7): 1111–24

  Abstract

  Transcranial magnetic resonance-guided focused ultrasound continues to gain traction as a noninvasive treatment option for a variety of pathologies. Focusing ultrasound through the skull can be accomplished by adding a phase correction to each element of a hemispherical transducer array. The phase corrections are determined with acoustic simulations that rely on speed of sound estimates derived from CT scans. While several studies have investigated the relationship between acoustic velocity and CT Hounsfield units (HUs), these studies have largely ignored the impact of X-ray energy, reconstruction method, and reconstruction kernel on the measured HU, and therefore the estimated velocity, and none have measured the relationship directly. In this paper, 91 ex vivo human skull fragments from two skulls are imaged by 80 CT scans with a variety of energies and reconstruction methods. The average HU from each fragment is found for each scan and correlated with the speed of sound measured using a through transmission technique in that fragment. As measured by the -squared value, the results show that CT is able to account for 23%-53% of the variation in velocity in the human skull. Both the X-ray energy and the reconstruction technique significantly alter the -squared value and the linear relationship between HU and speed of sound in bone. Accounting for these variations will lead to more accurate phase corrections and more efficient transmission of acoustic energy through the skull.

  View details for DOI 10.1109/TUFFC.2018.2827899

  View details for Web of Science ID 000436933000004

  View details for PubMedID 29993366

• Diffusion MRI tractography for improved transcranial MRI-guided focused ultrasound thalamotomy targeting for essential tremor. NeuroImage. Clinical Tian, Q., Wintermark, M., Jeffrey Elias, W., Ghanouni, P., Halpern, C. H., Henderson, J. M., Huss, D. S., Goubran, M., Thaler, C., Airan, R., Zeineh, M., Pauly, K. B., McNab, J. A. 2018; 19: 572–80

  Abstract

  Purpose: To evaluate the use of diffusion magnetic resonance imaging (MRI) tractography for neurosurgical guidance of transcranial MRI-guided focused ultrasound (tcMRgFUS) thalamotomy for essential tremor (ET).Materials and methods: Eight patients with medication-refractory ET were treated with tcMRgFUS targeting the ventral intermediate nucleus (Vim) of the thalamus contralateral to their dominant hand. Diffusion and structural MRI data and clinical evaluations were acquired pre-treatment and post-treatment. To identify the optimal target location, tractography was performed on pre-treatment diffusion MRI data between the treated thalamus and the hand-knob region of the ipsilateral motor cortex, the entire ipsilateral motor cortex and the contralateral dentate nucleus. The tractography-identified locations were compared to the lesion location delineated on 1 year post-treatment T2-weighted MR image. Their overlap was correlated with the clinical outcomes measured by the percentage change of the Clinical Rating Scale for Tremor scores acquired pre-treatment, as well as 1 month, 3 months, 6 months and 1 year post-treatment.Results: The probabilistic tractography was consistent from subject-to-subject and followed the expected anatomy of the thalamocortical radiation and the dentatothalamic tract. Higher overlap between the tractography-identified location and the tcMRgFUS treatment-induced lesion highly correlated with better treatment outcome (r = -0.929, -0.75, -0.643, p = 0.00675, 0.0663, 0.139 for the tractography between the treated thalamus and the hand-knob region of the ipsilateral motor cortex, the entire ipsilateral motor cortex and the contralateral dentate nucleus, respectively, at 1 year post-treatment). The correlation for the tractography between the treated thalamus and the hand-knob region of the ipsilateral motor cortex is the highest for all time points (r = -0.719, -0.976, -0.707, -0.929, p = 0.0519, 0.000397, 0.0595, 0.00675 at 1 month, 3 months, 6 months and 1 year post-treatment, respectively).Conclusion: Our data support the use of diffusion tractography as a complementary approach to current targeting methods for tcMRgFUS thalamotomy.

  View details for PubMedID 29984165

• Transcranial MRI-Guided Focused Ultrasound: A Review of the Technologic and Neurologic Applications AMERICAN JOURNAL OF ROENTGENOLOGY Ghanouni, P., Pauly, K. B., Elias, W. J., Henderson, J., Sheehan, J., Monteith, S., Wintermark, M. 2015; 205 (1): 150-159

  Abstract

  This article reviews the physical principles of MRI-guided focused ultra-sound and discusses current and potential applications of this exciting technology.MRI-guided focused ultrasound is a new minimally invasive method of targeted tissue thermal ablation that may be of use to treat central neuropathic pain, essential tremor, Parkinson tremor, and brain tumors. The system has also been used to temporarily disrupt the blood-brain barrier to allow targeted drug delivery to brain tumors.

  View details for DOI 10.2214/AJR.14.13632

  View details for PubMedID 26102394

• Transcranial ultrasound neuromodulation of the thalamic visual pathway in a large animal model and the dose‐response relationship with MR‐ARFI Scientific Reports Mohammadjavadi, M., Ash, R. T., Li, N., Gaur, P., Kubanek, J., Saenz, Y., Glover, G. H., Popelka, G. R., Norcia, A. M., Butts Pauly, K. 2022; 12: 19588

  View details for DOI 10.1038/s41598-022-20554-4

• Remote, brain region-specific control of choice behavior with ultrasonic waves. Science advances Kubanek, J. n., Brown, J. n., Ye, P. n., Pauly, K. B., Moore, T. n., Newsome, W. n. 2020; 6 (21): eaaz4193

  Abstract

  The ability to modulate neural activity in specific brain circuits remotely and systematically could revolutionize studies of brain function and treatments of brain disorders. Sound waves of high frequencies (ultrasound) have shown promise in this respect, combining the ability to modulate neuronal activity with sharp spatial focus. Here, we show that the approach can have potent effects on choice behavior. Brief, low-intensity ultrasound pulses delivered noninvasively into specific brain regions of macaque monkeys influenced their decisions regarding which target to choose. The effects were substantial, leading to around a 2:1 bias in choices compared to the default balanced proportion. The effect presence and polarity was controlled by the specific target region. These results represent a critical step towards the ability to influence choice behavior noninvasively, enabling systematic investigations and treatments of brain circuits underlying disorders of choice.

  View details for DOI 10.1126/sciadv.aaz4193

  View details for PubMedID 32671207

  View details for PubMedCentralID PMC7314556

• Improved Vim targeting for focused ultrasound ablation treatment of essential tremor: A probabilistic and patient-specific approach. Human brain mapping Su, J. H., Choi, E. Y., Tourdias, T. n., Saranathan, M. n., Halpern, C. H., Henderson, J. M., Pauly, K. B., Ghanouni, P. n., Rutt, B. K. 2020

  Abstract

  Magnetic resonance-guided focused ultrasound (MRgFUS) ablation of the ventral intermediate (Vim) thalamic nucleus is an incisionless treatment for essential tremor (ET). The standard initial targeting method uses an approximate, atlas-based stereotactic approach. We developed a new patient-specific targeting method to identify an individual's Vim and the optimal MRgFUS target region therein for suppression of tremor. In this retrospective study of 14 ET patients treated with MRgFUS, we investigated the ability of WMnMPRAGE, a highly sensitive and robust sequence for imaging gray matter-white matter contrast, to identify the Vim, FUS ablation, and a clinically efficacious region within the Vim in individual patients. We found that WMnMPRAGE can directly visualize the Vim in ET patients, segmenting this nucleus using manual or automated segmentation capabilities developed by our group. WMnMPRAGE also delineated the ablation's core and penumbra, and showed that all patients' ablation cores lay primarily within their Vim segmentations. We found no significant correlations between standard ablation features (e.g., ablation volume, Vim-ablation overlap) and 1-month post-treatment clinical outcome. We then defined a group-based probabilistic target, which was nonlinearly warped to individual brains; this target was located within the Vim for all patients. The overlaps between this target and patient ablation cores correlated significantly with 1-month clinical outcome (r = -.57, p = .03), in contrast to the standard target (r = -.23, p = .44). We conclude that WMnMPRAGE is a highly sensitive sequence for segmenting Vim and ablation boundaries in individual patients, allowing us to find a novel tremor-associated center within Vim and potentially improving MRgFUS treatment for ET.

  View details for DOI 10.1002/hbm.25157

  View details for PubMedID 32762005

• MR elastography frequency-dependent and independent parameters demonstrate accelerated decrease of brain stiffness in elder subjects. European radiology Lv, H. n., Kurt, M. n., Zeng, N. n., Ozkaya, E. n., Marcuz, F. n., Wu, L. n., Laksari, K. n., Camarillo, D. B., Pauly, K. B., Wang, Z. n., Wintermark, M. n. 2020

  Abstract

  To analyze the mechanical properties in different regions of the brain in healthy adults in a wide age range: 26 to 76 years old.We used a multifrequency magnetic resonance elastography (MRE) protocol to analyze the effect of age on frequency-dependent (storage and loss moduli, G' and G″, respectively) and frequency-independent parameters (μ1, μ2, and η, as determined by a standard linear solid model) of the cerebral parenchyma, cortical gray matter (GM), white matter (WM), and subcortical GM structures of 46 healthy male and female subjects. The multifrequency behavior of the brain and frequency-independent parameters were analyzed across different age groups.The annual change rate ranged from - 0.32 to - 0.36% for G' and - 0.43 to - 0.55% for G″ for the cerebral parenchyma, cortical GM, and WM. For the subcortical GM, changes in G' ranged from - 0.18 to - 0.23%, and G″ changed - 0.43%. Interestingly, males exhibited decreased elasticity, while females exhibited decreased viscosity with respect to age in some regions of subcortical GM. Significantly decreased values were also found in subjects over 60 years old.Values of G' and G″ at 60 Hz and the frequency-independent μ2 of the caudate, putamen, and thalamus may serve as parameters that characterize the aging effect on the brain. The decrease in brain stiffness accelerates in elderly subjects.• We used a multifrequency MRE protocol to assess changes in the mechanical properties of the brain with age. • Frequency-dependent (storage moduli G' and loss moduli G″) and frequency-independent (μ1, μ2, and η) parameters can bequantitatively measured by our protocol. • The decreased value of viscoelastic properties due to aging varies in different regions of subcortical GM in males and females, and the decrease in brain stiffness is accelerated in elderly subjects over 60 years old.

  View details for DOI 10.1007/s00330-020-07054-7

  View details for PubMedID 32683552

• Case Report on Deep Brain Stimulation Rescue After Suboptimal MR-Guided Focused Ultrasound Thalamotomy for Essential Tremor: A Tractography-Based Investigation. Frontiers in human neuroscience Saluja, S. n., Barbosa, D. A., Parker, J. J., Huang, Y. n., Jensen, M. R., Ngo, V. n., Santini, V. E., Pauly, K. B., Ghanouni, P. n., McNab, J. A., Halpern, C. H. 2020; 14: 191

  Abstract

  Essential tremor (ET) is the most prevalent movement disorder in adults, and can often be medically refractory, requiring surgical intervention. MRI-guided focused ultrasound (MRgFUS) is a less invasive procedure that uses ultrasonic waves to induce lesions in the ventralis intermedius nucleus (VIM) to treat refractory ET. As with all procedures for treating ET, optimal targeting during MRgFUS is essential for efficacy and durability. Various studies have reported cases of tremor recurrence following MRgFUS and long-term outcome data is limited to 3-4 years. We present a tractography-based investigation on a case of DBS rescue for medically refractory ET that was treated with MRgFUS that was interrupted due to the development of dysarthria during the procedure. After initial improvement, her hand tremor started to recur within 6 months after treatment, and bilateral DBS was performed targeting the VIM 24 months after MRgFUS. DBS induced long-term tremor control with monopolar stimulation. Diffusion MRI tractography was used to reconstruct the dentatorubrothalamic (DRTT) and corticothalmic (CTT) tracts being modulated by the procedures to understand the variability in efficacy between MRgFUS and DBS in treating ET in our patient. By comparing the MRgFUS lesion and DBS volume of activated tissue (VAT), we found that the MRgFUS lesion was located ventromedially to the VAT, and was less than 10% of the size of the VAT. While the lesion encompassed the same proportion of DRTT streamlines, it encompassed fewer CTT streamlines than the VAT. Our findings indicate the need for further investigation of targeting the CTT when using neuromodulatory procedures to treat refractory ET for more permanent tremor relief.

  View details for DOI 10.3389/fnhum.2020.00191

  View details for PubMedID 32676015

  View details for PubMedCentralID PMC7333679

• Prolonged heating in nontargeted tissue during MR-guided focused ultrasound of bone tumors JOURNAL OF MAGNETIC RESONANCE IMAGING Bitton, R. R., Webb, T. D., Pauly, K., Ghanouni, P. 2019; 50 (5): 1526–33

  View details for DOI 10.1002/jmri.26726

  View details for Web of Science ID 000490258000017

• Anatomic and Thermometric Analysis of Cranial Nerve Palsy after Laser Amygdalohippocampotomy for Mesial Temporal Lobe Epilepsy. Operative neurosurgery (Hagerstown, Md.) Huang, Y., Leung, S. A., Parker, J. J., Ho, A. L., Wintermark, M., Patel, S. H., Pauly, K. B., Kakusa, B. W., Beres, S. J., Henderson, J. M., Grant, G. A., Halpern, C. H. 2019

  Abstract

  BACKGROUND: Laser interstitial thermal therapy (LITT) is a minimally invasive therapy for treating medication-resistant mesial temporal lobe epilepsy. Cranial nerve (CN) palsy has been reported as a procedural complication, but the mechanism of this complication is not understood.OBJECTIVE: To identify the cause of postoperative CN palsy after LITT.METHODS: Four medial temporal lobe epilepsy patients with CN palsy after LITT were identified for comparison with 22 consecutive patients with no palsy. We evaluated individual variation in the distance between CN III and the uncus, and CN IV and the parahippocampal gyrus using preoperative T1- and T2-weighted magnetic resonance (MR) images. Intraoperative MR thermometry was used to estimate temperature changes.RESULTS: CN III (n=2) and CN IV palsies (n=2) were reported. On preoperative imaging, the majority of identified CN III (54%) and CN IV (43%) were located within 1 to 2 mm of the uncus and parahippocampal gyrus tissue border, respectively. Affected CN III and CN IV were more likely to be found<1 mm of the tissue border (PCNIII=.03, PCNIV<.01; chi-squared test). Retrospective assessment of thermal profile during ablation showed higher temperature rise along the mesial temporal lobe tissue border in affected CNs than unaffected CNs after controlling for distance (12.9°C vs 5.8°C; P=.03; 2-sample t-test).CONCLUSION: CN palsy after LITT likely results from direct heating of the respective CN running at extreme proximity to the mesial temporal lobe. Low-temperature thresholds set at the border of the mesial temporal lobe in patients whose CNs are at close proximity may reduce this risk.

  View details for DOI 10.1093/ons/opz279

  View details for PubMedID 31555820

• Elimination of peripheral auditory pathway activation does not affect motor responses from ultrasound neuromodulation BRAIN STIMULATION Mohammadjavadi, M., Ye, P., Xia, A., Brown, J., Popelka, G., Pauly, K. 2019; 12 (4): 901–10

  View details for DOI 10.1016/j.brs.2019.03.005

  View details for Web of Science ID 000472482500009

• Optimization of a Multifrequency Magnetic Resonance Elastography Protocol for the Human Brain JOURNAL OF NEUROIMAGING Kurt, M., Wu, L., Laksari, K., Ozkaya, E., Suar, Z. M., Lv, H., Epperson, K., Epperson, K., Sawyer, A. M., Camarillo, D., Pauly, K., Wintermark, M. 2019; 29 (4): 440–46

  View details for DOI 10.1111/jon.12619

  View details for Web of Science ID 000488852500003

• Optimization of a Multifrequency Magnetic Resonance Elastography Protocol for the Human Brain. Journal of neuroimaging : official journal of the American Society of Neuroimaging Kurt, M., Wu, L., Laksari, K., Ozkaya, E., Suar, Z. M., Lv, H., Epperson, K., Epperson, K., Sawyer, A. M., Camarillo, D., Pauly, K. B., Wintermark, M. 2019

  Abstract

  BACKGROUND AND PURPOSE: The brain's stiffness measurements from magnetic resonance elastography (MRE) strongly depend on actuation frequencies, which makes cross-study comparisons challenging. We performed a preliminary study to acquire optimal sets of actuation frequencies to accurately obtain rheological parameters for the whole brain (WB), white matter (WM), and gray matter (GM).METHODS: Six healthy volunteers aged between 26 and 72 years old went through MRE with a modified single-shot spin-echo echo planar imaging pulse sequence embedded with motion encoding gradients on a 3T scanner. Frequency-independent brain material properties and best-fit material model were determined from the frequency-dependent brain tissue response data (20 -80 Hz), by comparing four different linear viscoelastic material models (Maxwell, Kelvin-Voigt, Springpot, and Zener). During the material fitting, spatial averaging of complex shear moduli (G*) obtained under single actuation frequency was performed, and then rheological parameters were acquired. Since clinical scan time is limited, a combination of three actuation frequencies that would provide the most accurate approximation and lowest fitting error was determined for WB, WM, and GM by optimizing for the lowest Bayesian information criterion (BIC).RESULTS: BIC scores for the Zener and Springpot models showed these models approximate the multifrequency response of the tissue best. The best-fit frequency combinations for the reference Zener and Springpot models were identified to be 30-60-70 and 30-40-80 Hz, respectively, for the WB.CONCLUSIONS: Optimal sets of actuation frequencies to accurately obtain rheological parameters for WB, WM, and GM were determined from shear moduli measurements obtained via 3-dimensional direct inversion. We believe that our study is a first-step in developing a region-specific multifrequency MRE protocol for the human brain.

  View details for PubMedID 31056818

• Prolonged Heating in Nontargeted Tissue During MR-guided Focused Ultrasound of Bone Tumors. Journal of magnetic resonance imaging : JMRI Bitton, R. R., Webb, T. D., Pauly, K. B., Ghanouni, P. 2019

  Abstract

  BACKGROUND: Thermal dosimetry during MR-guided focused ultrasound (MRgFUS) of bone tumors underpredicts ablation zone. Intraprocedural understanding of heat accumulation near bone is needed to prevent undesired treatment of nontargeted tissue.HYPOTHESIS: Temperature decay rates predict prolonged, spatially varying heating during MRgFUS bone treatments.STUDY TYPE: Prospective case series.PATIENTS: Nine patients with localized painful bone tumors (five bone metastasis, four osteoid osteomas), were compared with five patients with uterine fibroid tumors treated using MRgFUS.FIELD STRENGTH/SEQUENCE: Proton resonance frequency shift thermometry using 2D-GRE with echo-planar imaging at 3T.ASSESSMENT: Tissue response was derived by fitting data from extended thermometry acquisitions to a decay model. Decay rates and time to peak temperature (TTP) were analyzed in segmented zones between the bone target and skin. Decay rates were used to calculate intersonication cooling times required to return to body temperature; these were compared against conventional system-mandated cooling times.STATISTICAL TESTS: Kolmogorov-Smirnov tests for normality, and Student's t-test was used to compare decay rates. Spatial TTP delay and predicted cooling times used Wilcoxon signed rank tests. P<0.05 was significant.RESULTS: Tissue decay rates in bone tumor patients were 3.5 times slower than those in patients with fibroids (taubone =0.037±0.012 vs. taufibroid =0.131±0.010, P<0.05). Spatial analysis showed slow decay rates effecting baseline temperature as far as 12mm away from the bone surface, tau4 =0.015±0.026 (median±interquartile range [IQR]). Tissue within 9mm of bone experienced delayed TTP (P<0.01). In the majority of bone tumor treatments, system-predicted intersonication cooling times were insufficient for nearby tissue to return to body temperature (P=0.03 in zone 4).DATA CONCLUSION: MRgFUS near bone is susceptible to long tissue decay rates, and unwanted cumulative heating up to 1.2cm from the surface of the bone. Knowledge of decay rates may be used to alter treatment planning and intraprocedural thermal monitoring protocols to account for prolonged heating by bone.LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2019.

  View details for PubMedID 30950554

• Impact of skull density ratio on efficacy and safety of magnetic resonance-guided focused ultrasound treatment of essential tremor. Journal of neurosurgery D'Souza, M. n., Chen, K. S., Rosenberg, J. n., Elias, W. J., Eisenberg, H. M., Gwinn, R. n., Taira, T. n., Chang, J. W., Lipsman, N. n., Krishna, V. n., Igase, K. n., Yamada, K. n., Kishima, H. n., Cosgrove, R. n., Rumià, J. n., Kaplitt, M. G., Hirabayashi, H. n., Nandi, D. n., Henderson, J. M., Butts Pauly, K. n., Dayan, M. n., Halpern, C. H., Ghanouni, P. n. 2019: 1–6

  Abstract

  OBJECTIVESkull density ratio (SDR) assesses the transparency of the skull to ultrasound. Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy in essential tremor (ET) patients with a lower SDR may be less effective, and the risk for complications may be increased. To address these questions, the authors analyzed clinical outcomes of MRgFUS thalamotomy based on SDRs.METHODSIn 189 patients, 3 outcomes were correlated with SDRs. Efficacy was based on improvement in Clinical Rating Scale for Tremor (CRST) scores 1 year after MRgFUS. Procedural efficiency was determined by the ease of achieving a peak voxel temperature of 54°C. Safety was based on the rate of the most severe procedure-related adverse event. SDRs were categorized at thresholds of 0.45 and 0.40, selected based on published criteria.RESULTSOf 189 patients, 53 (28%) had an SDR < 0.45 and 20 (11%) had an SDR < 0.40. There was no significant difference in improvement in CRST scores between those with an SDR ≥ 0.45 (58% ± 24%), 0.40 ≤ SDR < 0.45 (i.e., SDR ≥ 0.40 but < 0.45) (63% ± 27%), and SDR < 0.40 (49% ± 28%; p = 0.0744). Target temperature was achieved more often in those with an SDR ≥ 0.45 (p < 0.001). Rates of adverse events were lower in the groups with an SDR < 0.45 (p = 0.013), with no severe adverse events in these groups.CONCLUSIONSMRgFUS treatment of ET can be effectively and safely performed in patients with an SDR < 0.45 and an SDR < 0.40, although the procedure is more efficient when SDR ≥ 0.45.

  View details for PubMedID 31026836

• TESTING DIFFERENT COMBINATIONS OF ACOUSTIC PRESSURE AND DOSES OF QUINOLINIC ACID FOR INDUCTION OF FOCAL NEURON LOSS IN MICE USING TRANSCRANIAL LOW-INTENSITY FOCUSED ULTRASOUND ULTRASOUND IN MEDICINE AND BIOLOGY Zhang, Y., Liao, C., Qu, H., Huang, S., Jiang, H., Zhou, H., Abrams, E., Habte, F. G., Yuan, L., Bertram, E. H., Lee, K. S., Pauly, K., Buckmaster, P. S., Wintermark, M. 2019; 45 (1): 129–36

  View details for DOI 10.1016/j.ultrasmedbio.2018.08.023

  View details for Web of Science ID 000451607300015

• Enhanced microbubble contrast agent oscillation following 250kHz insonation. Scientific reports Ilovitsh, T., Ilovitsh, A., Foiret, J., Caskey, C. F., Kusunose, J., Fite, B. Z., Zhang, H., Mahakian, L. M., Tam, S., Butts-Pauly, K., Qin, S., Ferrara, K. W. 2018; 8 (1): 16347

  Abstract

  Microbubble contrast agents are widely used in ultrasound imaging and therapy, typically with transmission center frequencies in the MHz range. Currently, an ultrasound center frequency near 250kHz is proposed for clinical trials in which ultrasound combined with microbubble contrast agents is applied to open the blood brain barrier, since at this low frequency focusing through the human skull to a predetermined location can be performed with reduced distortion and attenuationcompared to higher frequencies. However, the microbubble vibrational response has not yet been carefully evaluated at this low frequency (an order of magnitude below the resonance frequency of these contrast agents). In the past, it was assumed that encapsulated microbubble expansion is maximized near the resonance frequency and monotonically decreases with decreasing frequency. Our results indicated that microbubble expansion was enhanced for 250kHz transmission as compared with the 1MHz center frequency. Following 250kHz insonation, microbubble expansion increased nonlinearly with increasing ultrasonic pressure, and was accurately predicted by either the modified Rayleigh-Plesset equation for a clean bubble or the Marmottant model of a lipid-shelledmicrobubble. The expansion ratio reached 30-fold with 250kHz at a peak negative pressure of 400kPa, as compared to a measured expansion ratio of 1.6 fold for 1MHz transmission at a similar peak negative pressure. Further, the range of peak negative pressure yielding stable cavitation in vitro was narrow (~100kPa) for the 250kHz transmission frequency. Blood brain barrier opening using in vivo transcranial ultrasound in mice followed the same trend as the in vitro experiments, and the pressure range for safe and effective treatment was 75-150kPa. For pressures above 150kPa, inertial cavitation and hemorrhage occurred. Therefore, we conclude that (1) at this low frequency, and for the large oscillations, lipid-shelled microbubbles can be approximately modeled as clean gas microbubbles and (2) the development of safe and successful protocols for therapeutic delivery to the brain utilizing 250kHz or a similar center frequency requires consideration of the narrow pressure window between stable and inertial cavitation.

  View details for PubMedID 30397280

• Enhanced microbubble contrast agent oscillation following 250 kHz insonation SCIENTIFIC REPORTS Ilovitsh, T., Ilovitsh, A., Foiret, J., Caskey, C. F., Kusunose, J., Fite, B. Z., Zhang, H., Mahakian, L. M., Tam, S., Butts-Pauly, K., Qin, S., Ferrara, K. W. 2018; 8

  View details for DOI 10.1038/s41598-018-34494-5

  View details for Web of Science ID 000449272100041

• Testing Different Combinations of Acoustic Pressure and Doses of Quinolinic Acid for Induction of Focal Neuron Loss in Mice Using Transcranial Low-Intensity Focused Ultrasound. Ultrasound in medicine & biology Zhang, Y., Liao, C., Qu, H., Huang, S., Jiang, H., Zhou, H., Abrams, E., Habte, F. G., Yuan, L., Bertram, E. H., Lee, K. S., Pauly, K. B., Buckmaster, P. S., Wintermark, M. 2018

  Abstract

  The goal of this study was to test different combinations of acoustic pressure and doses of quinolinic acid (QA) for producing a focal neuronal lesion in the murine hippocampus without causing unwanted damage to adjacent brain structures. Sixty male CD-1 mice were divided into 12 groups that underwent magnetic resonance-guided focused ultrasound at high (0.67 MPa), medium (0.5 MPa) and low (0.33 MPa) acoustic peak negative pressures and received QA at high (0.012 mmol), medium (0.006 mmol) and low (0.003 mmol) dosages. Neuronal loss occurred only when magnetic resonance-guided focused ultrasound with adequate acoustic power (0.67 or 0.5 MPa) was combined with QA. The animals subjected to the highest acoustic power had larger lesions than those treated with medium acoustic power, but two mice had evidence of bleeding. When the intermediate acoustic power was used, medium andhigh dosages of QA produced lesions larger than those produced by the low dosage.

  View details for PubMedID 30309748

• Brain stiffens post mortem JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS Weickenmeier, J., Kurt, M., Ozkaya, E., de Rooij, R., Ovaert, T. C., Ehman, R. L., Pauly, K., Kuhl, E. 2018; 84: 88–98

  View details for DOI 10.1016/j.jmbbm.2018.04.009

  View details for Web of Science ID 000441117800010

• Hearing out Ultrasound Neuromodulation. Neuron Airan, R. D., Butts Pauly, K. 2018; 98 (5): 875–77

  Abstract

  Many neuroscientists are excited regarding the potential of ultrasound to yield spatiotemporally precise and noninvasive modulation of arbitrary brain regions. Here, Guo etal. (2018) and Sato etal. (2018) show that applying ultrasound to rodent brains activates acoustic responses more prominently than eliciting neuromodulation directly, suggesting potential confounds of ultrasound neuromodulation experiments.

  View details for PubMedID 29879389

• Hearing out Ultrasound Neuromodulation NEURON Airan, R. D., Pauly, K. 2018; 98 (5): 875–77

  View details for DOI 10.1016/j.neuron.2018.05.031

  View details for Web of Science ID 000436585500004

• A spiral-based volumetric acquisition for MR temperature imaging MAGNETIC RESONANCE IN MEDICINE Fielden, S. W., Feng, X., Zhao, L., Miller, G., Geeslin, M., Dallapiazza, R. F., Elias, W., Wintermark, M., Pauly, K., Meyer, C. H. 2018; 79 (6): 3122–27

  Abstract

  To develop a rapid pulse sequence for volumetric MR thermometry.Simulations were carried out to assess temperature deviation, focal spot distortion/blurring, and focal spot shift across a range of readout durations and maximum temperatures for Cartesian, spiral-out, and retraced spiral-in/out (RIO) trajectories. The RIO trajectory was applied for stack-of-spirals 3D imaging on a real-time imaging platform and preliminary evaluation was carried out compared to a standard 2D sequence in vivo using a swine brain model, comparing maximum and mean temperatures measured between the two methods, as well as the temporal standard deviation measured by the two methods.In simulations, low-bandwidth Cartesian trajectories showed substantial shift of the focal spot, whereas both spiral trajectories showed no shift while maintaining focal spot geometry. In vivo, the 3D sequence achieved real-time 4D monitoring of thermometry, with an update time of 2.9-3.3 s.Spiral imaging, and RIO imaging in particular, is an effective way to speed up volumetric MR thermometry. Magn Reson Med 79:3122-3127, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

  View details for PubMedID 29115692

• Brain stiffens post mortem. Journal of the mechanical behavior of biomedical materials Weickenmeier, J., Kurt, M., Ozkaya, E., de Rooij, R., Ovaert, T. C., Ehman, R. L., Butts Pauly, K., Kuhl, E. 2018; 84: 88–98

  Abstract

  Alterations in brain rheology are increasingly recognized as a diagnostic marker for various neurological conditions. Magnetic resonance elastography now allows us to assess brain rheology repeatably, reproducibly, and non-invasively in vivo. Recent elastography studies suggest that brain stiffness decreases one percent per year during normal aging, and is significantly reduced in Alzheimer's disease and multiple sclerosis. While existing studies successfully compare brain stiffnesses across different populations, they fail to provide insight into changes within the same brain. Here we characterize rheological alterations in one and the same brain under extreme metabolic changes: alive and dead. Strikingly, the storage and loss moduli of the cerebrum increased by 26% and 60% within only three minutes post mortem and continued to increase by 40% and 103% within 45 minutes. Immediate post mortem stiffening displayed pronounced regional variations; it was largest in the corpus callosum and smallest in the brainstem. We postulate that post mortem stiffening is a manifestation of alterations in polarization, oxidation, perfusion, and metabolism immediately after death. Our results suggest that the stiffness of our brain-unlike any other organ-is a dynamic property that is highly sensitive to the metabolic environment. Our findings emphasize the importance of characterizing brain tissue in vivo and question the relevance of ex vivo brain tissue testing as a whole. Knowing the true stiffness of the living brain has important consequences in diagnosing neurological conditions, planning neurosurgical procedures, and modeling the brain's response to high impact loading.

  View details for PubMedID 29754046

• High sensitivity MR acoustic radiation force imaging using transition band balanced steady-state free precession MAGNETIC RESONANCE IN MEDICINE Zheng, Y., Marx, M., Miller, G., Pauly, K. 2018; 79 (3): 1532–37

  Abstract

  MR acoustic radiation force imaging (MR-ARFI) provides a method to visualize the focal spot of a focused ultrasound (FUS) beam without introducing a significant temperature rise. With conventional spoiled MR-ARFI pulse sequences, the ARFI phase always equals the motion-encoded phase. In this work, MR-ARFI using transition band balanced steady-state free precession (bSSFP) is presented, which improves the sensitivity of MR-ARFI with high acquisition speed.Motion-encoding gradients (MEG) are inserted into bSSFP sequences for MR-ARFI. By applying an ultrasound pulse during the MEG, motion-encoded phase is generated, which leads to an amplified change in the image phase when operating in the bSSFP transition band. MR-ARFI was performed on a homemade gel phantom using both the proposed technique and a spoiled gradient echo ARFI sequence with identical MEG and FUS, and ARFI images were compared.The bSSFP-ARFI sequence generated an ARFI image phase that is more than 5 times larger than the motion-encoded phase in a few seconds with 2DFT readout. By keeping FUS pulses as short as 1.45 ms, temperature rise was insignificant during the measurement.bSSFP-ARFI has enhanced sensitivity compared with conventional MR-ARFI pulse sequences and could provide an efficient way to visualize the focal spot. Magn Reson Med 79:1532-1537, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

  View details for PubMedID 28631853

• Printed Receive Coils with High Acoustic Transparency for Magnetic Resonance Guided Focused Ultrasound SCIENTIFIC REPORTS Corea, J., Ye, P., Seo, D., Butts-Pauly, K., Arias, A., Lustig, M. 2018; 8: 3392

  Abstract

  In magnetic resonance guided focused ultrasound (MRgFUS) therapy sound waves are focused through the body to selectively ablate difficult to access lesions and tissues. A magnetic resonance imaging (MRI) scanner non-invasively tracks the temperature increase throughout the tissue to guide the therapy. In clinical MRI, tightly fitted hardware comprised of multichannel coil arrays are required to capture high quality images at high spatiotemporal resolution. Ablating tissue requires a clear path for acoustic energy to travel but current array materials scatter and attenuate acoustic energy. As a result coil arrays are placed outside of the transducer, clear of the beam path, compromising imaging speed, resolution, and temperature accuracy of the scan. Here we show that when coil arrays are fabricated by additive manufacturing (i.e., printing), they exhibit acoustic transparency as high as 89.5%. This allows the coils to be placed in the beam path increasing the image signal to noise ratio (SNR) five-fold in phantoms and volunteers. We also characterize printed coil materials properties over time when submerged in the water required for acoustic coupling. These arrays offer high SNR and acceleration capabilities, which can address current challenges in treating head and abdominal tumors allowing MRgFUS to give patients better outcomes.

  View details for PubMedID 29467432

• Magnetic resonance elastography of the brain: A comparison between pigs and humans JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS Weickenmeier, J., Kurt, M., Ozkaya, E., Wintermark, M., Pauly, K., Kuhl, E. 2018; 77: 702–10

  Abstract

  Magnetic resonance elastography holds promise as a non-invasive, easy-to-use, in vivo biomarker for neurodegenerative diseases. Throughout the past decade, pigs have gained increased popularity as large animal models for human neurodegeneration. However, the volume of a pig brain is an order of magnitude smaller than the human brain, its skull is 40% thicker, and its head is about twice as big. This raises the question to which extent established vibration devices, actuation frequencies, and analysis tools for humans translate to large animal studies in pigs. Here we explored the feasibility of using human brain magnetic resonance elastography to characterize the dynamic properties of the porcine brain. In contrast to humans, where vibration devices induce an anterior-posterior displacement recorded in transverse sections, the porcine anatomy requires a dorsal-ventral displacement recorded in coronal sections. Within these settings, we applied a wide range of actuation frequencies, from 40Hz to 90Hz, and recorded the storage and loss moduli for human and porcine brains. Strikingly, we found that optimal actuation frequencies for humans translate one-to-one to pigs and reliably generate shear waves for elastographic post-processing. In a direct comparison, human and porcine storage and loss moduli followed similar trends and increased with increasing frequency. When translating these frequency-dependent storage and loss moduli into the frequency-independent stiffnesses and viscosities of a standard linear solid model, we found human values of μ1=1.3kPa, μ2=2.1kPa, and η=0.025kPas and porcine values of μ1=2.0kPa, μ2=4.9kPa, and η=0.046kPas. These results suggest that living human brain is softer and less viscous than dead porcine brain. Our study compares, for the first time, magnetic resonance elastography in human and porcine brains, and paves the way towards systematic interspecies comparison studies and ex vivo validation of magnetic resonance elastography as a whole.

  View details for PubMedID 28919161

• Diffusion MRI tractography for improved transcranial MRI-guided focused ultrasound thalamotomy targeting for essential tremor NEUROIMAGE-CLINICAL Tian, Q., Wintermark, M., Elias, W., Ghanouni, P., Halpern, C. H., Henderson, J. M., Huss, D. S., Goubran, M., Thaler, C., Airan, R., Zeineh, M., Pauly, K., McNab, J. A. 2018; 19: 572–80

  View details for DOI 10.1016/j.nicl.2018.05.010

  View details for Web of Science ID 000441936300059

• MRI monitoring of focused ultrasound sonications near metallic hardware. Magnetic resonance in medicine Weber, H. n., Ghanouni, P. n., Pascal-Tenorio, A. n., Pauly, K. B., Hargreaves, B. A. 2018; 80 (1): 259–71

  Abstract

  To explore the temperature-induced signal change in two-dimensional multi-spectral imaging (2DMSI) for fast thermometry near metallic hardware to enable MR-guided focused ultrasound surgery (MRgFUS) in patients with implanted metallic hardware.2DMSI was optimized for temperature sensitivity and applied to monitor focus ultrasound surgery (FUS) sonications near metallic hardware in phantoms and ex vivo porcine muscle tissue. Further, we evaluated its temperature sensitivity for in vivo muscle in patients without metallic hardware. In addition, we performed a comparison of temperature sensitivity between 2DMSI and conventional proton-resonance-frequency-shift (PRFS) thermometry at different distances from metal devices and different signal-to-noise ratios (SNR).2DMSI thermometry enabled visualization of short ultrasound sonications near metallic hardware. Calibration using in vivo muscle yielded a constant temperature sensitivity for temperatures below 43 °C. For an off-resonance coverage of ± 6 kHz, we achieved a temperature sensitivity of 1.45%/K, resulting in a minimum detectable temperature change of ∼2.5 K for an SNR of 100 with a temporal resolution of 6 s per frame.The proposed 2DMSI thermometry has the potential to allow MR-guided FUS treatments of patients with metallic hardware and therefore expand its reach to a larger patient population. Magn Reson Med 80:259-271, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

  View details for PubMedID 29215150

  View details for PubMedCentralID PMC5876098

• Treatment of Low-Flow Vascular Malformations of the Extremities Using MR-Guided High Intensity Focused Ultrasound: Preliminary Experience JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY Ghanouni, P., Kishore, S., Lungren, M. P., Bitton, R., Chan, L., Avedian, R., Bazzocchi, A., Pauly, K., Napoli, A., Hovsepian, D. M. 2017; 28 (12): 1739–44

  Abstract

  Five patients with painful vascular malformations of the extremities that were refractory to standard treatment and were confirmed as low-flow malformations on dynamic contrast-enhanced magnetic resonance (MR) imaging were treated with MR imaging-guided high intensity focused ultrasound. Daily maximum numeric rating scale scores for pain improved from 8.4 ± 1.5 to 1.6 ± 2.2 (P = .004) at a median follow-up of 9 months (range, 4-36 mo). The size of the vascular malformations decreased on follow-up MR imaging (median enhancing volume, 8.2 mL [0.7-10.1 mL] before treatment; 0 mL [0-2.3 mL] after treatment; P = .018) at a median follow-up of 5 months (range, 3-36 mo). No complications occurred.

  View details for PubMedID 29157478

  View details for PubMedCentralID PMC5726422

• Cost-effectiveness of focused ultrasound, radiosurgery, and DBS for essential tremor. Movement disorders Ravikumar, V. K., Parker, J. J., Hornbeck, T. S., Santini, V. E., Pauly, K. B., Wintermark, M., Ghanouni, P., Stein, S. C., Halpern, C. H. 2017

  Abstract

  Essential tremor remains a very common yet medically refractory condition. A recent phase 3 study demonstrated that magnetic resonance-guided focused ultrasound thalamotomy significantly improved upper limb tremor. The objectives of this study were to assess this novel therapy's cost-effectiveness compared with existing procedural options.Literature searches of magnetic resonance-guided focused ultrasound thalamotomy, DBS, and stereotactic radiosurgery for essential tremor were performed. Pre- and postoperative tremor-related disability scores were collected from 32 studies involving 83 magnetic resonance-guided focused ultrasound thalamotomies, 615 DBSs, and 260 stereotactic radiosurgery cases. Utility, defined as quality of life and derived from percent change in functional disability, was calculated; Medicare reimbursement was employed as a proxy for societal cost. Medicare reimbursement rates are not established for magnetic resonance-guided focused ultrasound thalamotomy for essential tremor; therefore, reimbursements were estimated to be approximately equivalent to stereotactic radiosurgery to assess a cost threshold. A decision analysis model was constructed to examine the most cost-effective option for essential tremor, implementing meta-analytic techniques.Magnetic resonance-guided focused ultrasound thalamotomy resulted in significantly higher utility scores compared with DBS (P < 0.001) or stereotactic radiosurgery (P < 0.001). Projected costs of magnetic resonance-guided focused ultrasound thalamotomy were significantly less than DBS (P < 0.001), but not significantly different from radiosurgery.Magnetic resonance-guided focused ultrasound thalamotomy is cost-effective for tremor compared with DBS and stereotactic radiosurgery and more effective than both. Even if longer follow-up finds changes in effectiveness or costs, focused ultrasound thalamotomy will likely remain competitive with both alternatives. © 2017 International Parkinson and Movement Disorder Society.

  View details for DOI 10.1002/mds.26997

  View details for PubMedID 28370272

• MR Thermometry Near Metallic Devices Using Multispectral Imaging MAGNETIC RESONANCE IN MEDICINE Weber, H., Taviani, V., Yoon, D., Ghanouni, P., Pauly, K. B., Hargreaves, B. A. 2017; 77 (3): 1162-1169

  Abstract

  The lack of a technique for MR thermometry near metal excludes a growing patient population from promising treatments such as MR-guided focused ultrasound therapy. Here we explore the feasibility of multispectral imaging (MSI) for noninvasive temperature measurement in the presence of strong field inhomogeneities by exploiting the temperature dependency of the T1 relaxation time.A two-dimensional inversion-recovery-prepared MSI pulse sequence (2DMSI) was implemented for artifact-reduced T1 mapping near metal. A series of T1 maps was acquired in a metallic implant phantom while increasing the phantom temperature. The measured change in T1 was analyzed with respect to the phantom temperature. For comparison, proton resonance frequency shift (PRFS) thermometry was performed.2DMSI achieved artifact-reduced, single-slice T1 mapping in the presence of strong off-resonance with a spatial resolution of 1.9 mm in-plane and a temporal resolution of 5 min. The maps enabled temperature measurements over a range of 30°C with an uncertainty below 1.4°C. The quality of the resulting temperature maps was independent of the distance from the metal, whereas the PRFS-based temperature measurements were increasingly impaired with increasing off-resonance.We demonstrated the ability to noninvasively measure temperature near metal using MSI and the T1 temperature sensitivity. Magn Reson Med, 2016. © 2016 Wiley Periodicals, Inc.

  View details for DOI 10.1002/mrm.26203

  View details for Web of Science ID 000397407800025

• Magnetic resonance-guided focused ultrasound treatment of extra-abdominal desmoid tumors: a retrospective multicenter study EUROPEAN RADIOLOGY Ghanouni, P., Dobrotwir, A., Bazzocchi, A., Bucknor, M., Bitton, R., Rosenberg, J., Telischak, K., Busacca, M., Ferrari, S., Albisinni, U., Walters, S., Gold, G., Ganjoo, K., Napoli, A., Pauly, K. B., Avedian, R. 2017; 27 (2): 732-740

  Abstract

  To assess the feasibility, safety and preliminary efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of extra-abdominal desmoid tumours.Fifteen patients with desmoid fibromatosis (six males, nine females; age range, 7-66 years) were treated with MRgFUS, with seven patients requiring multiple treatments (25 total treatments). Changes in viable and total tumour volumes were measured after treatment. Efficacy was evaluated using an exact one-sided Wilcoxon test to determine if the median reduction in viable tumour measured immediately after initial treatment exceeded a threshold of 50 % of the targeted volume. Median decrease after treatment of at least two points in numerical rating scale (NRS) worst and average pain scores was tested with an exact one-sided Wilcoxon test. Adverse events were recorded.After initial MRgFUS treatment, median viable targeted tumour volume decreased 63 %, significantly beyond our efficacy threshold (P = 0.0013). Median viable total tumour volume decreased (105 mL [interquartile range {IQR}, 217 mL] to 54 mL [IQR, 92 mL]) and pain improved (worst scores, 7.5 ± 1.9 vs 2.7 ± 2.6, P = 0.027; average scores, 6 ± 2.3 vs 1.3 ± 2, P = 0.021). Skin burn was the most common complication.MRgFUS significantly and durably reduced viable tumour volume and pain in this series of 15 patients with extra-abdominal desmoid fibromatosis.• Retrospective four-centre study shows MRgFUS safely and effectively treats extra-abdominal desmoid tumours • This non-invasive procedure can eradicate viable tumour in some cases • Alternatively, MRgFUS can provide durable control of tumour growth through repeated treatments • Compared to surgery or radiation, MRgFUS has relatively mild side effects.

  View details for DOI 10.1007/s00330-016-4376-5

  View details for Web of Science ID 000392142000034

• Improved cortical bone specificity in UTE MR Imaging MAGNETIC RESONANCE IN MEDICINE Johnson, E. M., Vyas, U., Ghanouni, P., Pauly, K. B., Pauly, J. M. 2017; 77 (2): 684-695

  Abstract

  Methods for direct visualization of compact bone using MRI have application in several "MR-informed" technologies, such as MR-guided focused ultrasound, MR-PET reconstruction and MR-guided radiation therapy. The specificity of bone imaging can be improved by manipulating image sensitivity to Bloch relaxation phenomena, facilitating distinction of bone from other tissues detected by MRI.From Bloch equation dynamics, excitation pulses suitable for creating specific sensitivity to short-T2 magnetization from cortical bone are identified. These pulses are used with UTE subtraction demonstrate feasibility of MR imaging of compact bone with positive contrast.MR images of bone structures are acquired with contrast similar to that observed in x-ray CT images. Through comparison of MR signal intensities with CT Hounsfield units of the skull, the similarity of contrast is quantified. The MR technique is also demonstrated in other regions of the body that are relevant for interventional procedures, such as the shoulder, pelvis and leg.Matching RF excitation pulses to relaxation rates improves the specificity to bone of short-T2 contrast. It is demonstrated with a UTE sequence to acquire images of cortical bone with positive contrast, and the contrast is verified by comparison with x-ray CT. Magn Reson Med, 2016. © 2016 Wiley Periodicals, Inc.

  View details for DOI 10.1002/mrm.26160

  View details for Web of Science ID 000394544700025

  View details for PubMedCentralID PMC5040625

• A meta-analysis of palliative treatment of pancreatic cancer with high intensity focused ultrasound. Journal of therapeutic ultrasound Dababou, S., Marrocchio, C., Rosenberg, J., Bitton, R., Pauly, K. B., Napoli, A., Hwang, J. H., Ghanouni, P. 2017; 5: 9-?

  Abstract

  Pancreatic adenocarcinoma is currently the fourth-leading cause of cancer-related death. Up to 60-90% of patients with advanced disease suffer cancer-related pain, severely impacting their quality of life. Current management involves primarily pharmacotherapy with opioid narcotics and celiac plexus neurolysis; unfortunately, both approaches offer transient relief and cause undesired side-effects. High intensity focused ultrasound (HIFU) is a non-invasive thermal ablation technique that has been used to treat pancreatic cancer. This meta-analysis aims to evaluate the role of HIFU in pain palliation of advanced unresectable pancreatic adenocarcinoma.An electronic search was performed in PubMed Medline database up to the end of July 2016, for unresectable pancreatic cancer pain palliation with HIFU. Pertinent studies were identified through the PubMed search engine using the following keywords: HIFU, pancreas, pancreatic cancer, pain and palliation. Additional studies were included after manual search of the selected bibliographies. Pain palliation results reported in each study were analyzed using a logit-transformed random-effects model using the inverse variance method, with the DerSimonian-Laird estimator for τ(2), and Cochran's Q test for heterogeneity among studies. The I(2) was calculated to assess the percentage of the total variability in the different effect size estimates that can be attributed to heterogeneity among the true effects. A rank correlation test of funnel plot asymmetry was done to assess possible publication bias.The meta-analysis includes a total number of 23 studies with 865 patients, 729 with pancreatic cancer. The population enrolled ranges from 3 patients in the smallest series, up to 61 in the largest study. τ(2) (variance among studies) was 0.195, and I(2) (percentage of variation among studies) was 40% (95% CI: 1-64%); the Q test p-value was 0.026, indicating significant heterogeneity among studies. Among 639 patients treated with HIFU, 567 complained of pancreatic pain before the treatment and 459 patients experienced partial or complete pain relief after treatment. The random effects estimate of the proportion of patients with pain reduction was 0.81 (95% CI: 0.76-86).HIFU appears to be an effective tool for pain palliation in advanced pancreatic cancer. Studies assessing treatment in patients with pancreatic adenocarcinoma are limited by factors such as small sample sizes and heterogeneity in clinical definitions and assessments. Prospective randomized and standardized studies are necessary to confirm the effectiveness of HIFU in relieving pain, and to evaluate for any potential impact on tumor control and patient survival.

  View details for DOI 10.1186/s40349-017-0080-4

  View details for PubMedID 28373906

• A 1-MHz 2-D CMUT Array for HIFU Thermal Ablation Yoon, H., Vaithilingam, S., Park, K., Nikoozadeh, A., Firouzi, K., Choe, J., Watkins, R. D., Oguz, H., Kupnik, M., Pauly, K., Khuri-Yakub, P., Fowlkes, J. B., Salgaonkar, V. A. AMER INST PHYSICS. 2017

  View details for DOI 10.1063/1.4977622

  View details for Web of Science ID 000405773600013

• Correlation Of p63 Immunohistochemistry With Histology And Contrast Enhanced MRI In Characteristic Lesions Induced By Minimally Invasive Thermal Treatments In A Dog Prostate Pascal, A., Butts-Pauly, K., Plata, J., Sommer, G., Daniel, B., Bouley, D. M., Fowlkes, J. B., Salgaonkar, V. A. AMER INST PHYSICS. 2017

  View details for DOI 10.1063/1.4977670

  View details for Web of Science ID 000405773600061

• Experimental Investigations of an Endoluminal Ultrasound Applicator for MR-guided Thermal Therapy of Pancreatic Cancer Adams, M., Salgaonkar, V., Jones, P., Plata, J., Chen, H., Pauly, K., Sommer, G., Diederich, C., Fowlkes, J. B., Salgaonkar, V. A. AMER INST PHYSICS. 2017

  View details for DOI 10.1063/1.4977620

  View details for Web of Science ID 000405773600011

• Transcranial MRI-guided high-intensity focused ultrasound for treatment of essential tremor: A pilot study on the correlation between lesion size, lesion location, thermal dose, and clinical outcome. Journal of magnetic resonance imaging : JMRI Federau, C. n., Goubran, M. n., Rosenberg, J. n., Henderson, J. n., Halpern, C. H., Santini, V. n., Wintermark, M. n., Butts Pauly, K. n., Ghanouni, P. n. 2017

  Abstract

  Transcranial MR-guided high-intensity focused ultrasound (tcMRgFUS) is a promising noninvasive method to treat medication-refractory essential tremor.To define the correlation between lesion size after ablation, thermal dose, and clinical outcome in tcMRgFUS treatment of essential tremor.Retrospective.Eight patients with medication-refractory essential tremor were treated using a tcMRgFUS system at 3T.T2 -weighted images were acquired immediately and at 1 year posttreatment at 3T.An atlas of the thalamic nuclei and dose maps were warped to the posttreatment images. The thermal dose, the immediate posttreatment lesion volume and 1-year final lesion volume, and the volumes confined inside the ventral division of the ventral lateral posterior thalamic nucleus (VLpv) were correlated to clinical outcome at 1 month and 1 year using Pearson's coefficient. The spatial region of treatment correlating with maximal clinical outcome was derived in a normalized space from average maps of clinical tremor score improvement at 1 year.Statistical significance was assessed using the Wilcoxon two-tailed rank test.The correlations between thermal dose, lesion volume posttreatment and at 1 year, and outcome at 1 year were good (r = 0.73, 0.65, 0.73, respectively), and were slightly better than at 1 month (r = 0.57, 0.49, 0.65). Reducing the measurement to include only the portion within the VLpv did not significantly modify the correlations (P = 0.09). The center of the spatial region of treatment was found in the anterior commissure - posterior commissure plane, 14.3 mm lateral from the midline, and 8.3 mm rostral to the posterior commissure.In this pilot study a good correlation was found between the size of the lesion, the thermal dose, and the clinical outcome in patients treated for essential tremor with ablation of the VLpv with tcMRgFUS.1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2017.

  View details for PubMedID 29076274

• Ex Vivo HIFU Experiments Using a 32 x 32-Element CMUT Array IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Yoon, H., Chang, C., Jang, J. H., Bhuyan, A., Choe, J. W., Nikoozadeh, A., Watkins, R. D., Stephens, D. N., Pauly, K. B., Khuri-Yakub, B. T. 2016; 63 (12): 2150-2158

  Abstract

  High-intensity focused ultrasound (HIFU) has been used as noninvasive treatment for various diseases. For these therapeutic applications, capacitive micromachined ultrasonic transducers (CMUTs) have advantages that make them potentially preferred transducers over traditional piezoelectric transducers. In this paper, we present the design and the fabrication process of an 8 ×8 -mm (2) 32 ×32 -element 2-D CMUT array for HIFU applications. To reduce the system complexity for addressing the 1024 transducer elements, we propose to group the CMUT array elements into eight HIFU channels based on the phase delay from the CMUT element to the targeted focal point. Designed to focus at an 8-mm depth with a 5-MHz exciting frequency, this grouping scheme was realized using a custom application-specific integrated circuit. With a 40-V dc bias and a 60-V peak-to-peak ac excitation, the surface pressure was measured 1.2 MPa peak-to-peak and stayed stable for a long enough time to create a lesion. With this dc and ac voltage combination, the measured peak-to-peak output pressure at the focus was 8.5 MPa, which is expected to generate a lesion in a minute according to the temperature simulation. The following ex vivo tissue experiments successfully demonstrated its capability to make lesions in both bovine muscle and liver tissue.

  View details for DOI 10.1109/TUFFC.2016.2606126

  View details for Web of Science ID 000391550200014

  View details for PubMedCentralID PMC5241055

• Specialized volumetric thermometry for improved guidance of MRgFUS in brain. Magnetic resonance in medicine Marx, M., Ghanouni, P., Butts Pauly, K. 2016

  Abstract

  MR thermometry is critical for safe and effective transcranial focused ultrasound. The current single-slice MR thermometry sequence cannot achieve all desired treatment monitoring requirements. We propose an approach in which the imaging requirements of different aspects of treatment monitoring are met by optimizing multiple sequences.Imaging requirements were determined for three stages of MR-guided focused ultrasound brain treatment: 1) focal spot localization, 2) focal spot monitoring, and 3) background monitoring. Multiple-echo spiral thermometry sequences were optimized for each set of requirements and then validated with in vivo signal-to-noise ratio measurements and with phantom heating experiments.Each of the proposed sequences obtained better precision than the current two-dimensional Fourier transform (2DFT) thermometry sequence. Five-slice focal spot localization achieved two-fold better resolution with 1.9-fold better precision but two-fold longer acquisition compared to 2DFT. Five-slice focal monitoring achieved 2.1-fold better precision with similar speed but 12% larger voxels than 2DFT. Full-brain background monitoring was demonstrated in both axial (7.1 s) and sagittal (11.4 s) orientations. Phantom heating time curves were consistent across all sequences after correcting for resolution.Multiple-echo spiral imaging significantly improves MR thermometry efficiency, enabling multiple-slice monitoring. Optimizing multiple specialized sequences provides better performance than can be achieved by any single sequence. Magn Reson Med, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

  View details for DOI 10.1002/mrm.26385

  View details for PubMedID 27699844

• Predicting variation in subject thermal response during transcranial magnetic resonance guided focused ultrasound surgery: Comparison in seventeen subject datasets. Medical physics Vyas, U., Ghanouni, P., Halpern, C. H., Elias, J., Pauly, K. B. 2016; 43 (9): 5170-?

  Abstract

  In transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) treatments, the acoustic and spatial heterogeneity of the skull cause reflection, absorption, and scattering of the acoustic beams. These effects depend on skull-specific parameters and can lead to patient-specific thermal responses to the same transducer power. In this work, the authors develop a simulation tool to help predict these different experimental responses using 3D heterogeneous tissue models based on the subject CT images. The authors then validate and compare the predicted skull efficiencies to an experimental metric based on the subject thermal responses during tcMRgFUS treatments in a dataset of seventeen human subjects.Seventeen human head CT scans were used to create tissue acoustic models, simulating the effects of reflection, absorption, and scattering of the acoustic beam as it propagates through a heterogeneous skull. The hybrid angular spectrum technique was used to model the acoustic beam propagation of the InSightec ExAblate 4000 head transducer for each subject, yielding maps of the specific absorption rate (SAR). The simulation assumed the transducer was geometrically focused to the thalamus of each subject, and the focal SAR at the target was used as a measure of the simulated skull efficiency. Experimental skull efficiency for each subject was calculated using the thermal temperature maps from the tcMRgFUS treatments. Axial temperature images (with no artifacts) were reconstructed with a single baseline, corrected using a referenceless algorithm. The experimental skull efficiency was calculated by dividing the reconstructed temperature rise 8.8 s after sonication by the applied acoustic power.The simulated skull efficiency using individual-specific heterogeneous models predicts well (R(2) = 0.84) the experimental energy efficiency.This paper presents a simulation model to predict the variation in thermal responses measured in clinical ctMRGFYS treatments while being computationally feasible.

  View details for DOI 10.1118/1.4955436

  View details for PubMedID 27587047

• Improved MRI thermometry with multiple-echo spirals. Magnetic resonance in medicine Marx, M., Butts Pauly, K. 2016; 76 (3): 747-756

  Abstract

  Low-bandwidth PRF shift thermometry is used to guide HIFU ablation treatments. Low sampling bandwidth is needed for high signal-to-noise ratio with short acquisition times, but can lead to off-resonance artifacts. In this work, improved multiple-echo thermometry is presented that allows for high bandwidth and reduced artifacts. It is also demonstrated with spiral sampling, to improve the trade-off between resolution, speed, and measurement precision.Four multiple-echo thermometry sequences were tested in vivo, one using two-dimensional Fourier transform (2DFT) sampling and three using spirals. The spiral sequences were individually optimized for resolution, for speed, and for precision. Multifrequency reconstruction was used to correct for off-resonance spiral artifacts. Additionally, two different multiecho temperature reconstructions were compared.Weighted combination of per-echo phase differences gave significantly better precision than least squares off-resonance estimation. Multiple-echo 2DFT sequence obtained precision similar to single-echo 2DFT, while greatly increasing sampling bandwidth. The multiecho spiral acquisitions achieved 2× better resolution, 2.9× better uncertainty, or 3.4× faster acquisition time, without negatively impacting the other two design parameters as compared to single-echo 2DFT.Multiecho spiral thermometry greatly improves the capabilities of temperature monitoring, and could improve transcranial treatment monitoring capabilities. Magn Reson Med 76:747-756, 2016. © 2015 Wiley Periodicals, Inc.

  View details for DOI 10.1002/mrm.25914

  View details for PubMedID 26332512

  View details for PubMedCentralID PMC4772149

• A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor. New England journal of medicine Elias, W. J., Lipsman, N., Ondo, W. G., Ghanouni, P., Kim, Y. G., Lee, W., Schwartz, M., Hynynen, K., Lozano, A. M., Shah, B. B., Huss, D., Dallapiazza, R. F., Gwinn, R., Witt, J., Ro, S., Eisenberg, H. M., Fishman, P. S., Gandhi, D., Halpern, C. H., Chuang, R., Butts Pauly, K., Tierney, T. S., Hayes, M. T., Cosgrove, G. R., Yamaguchi, T., Abe, K., Taira, T., Chang, J. W. 2016; 375 (8): 730-739

  Abstract

  Uncontrolled pilot studies have suggested the efficacy of focused ultrasound thalamotomy with magnetic resonance imaging (MRI) guidance for the treatment of essential tremor.We enrolled patients with moderate-to-severe essential tremor that had not responded to at least two trials of medical therapy and randomly assigned them in a 3:1 ratio to undergo unilateral focused ultrasound thalamotomy or a sham procedure. The Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire were administered at baseline and at 1, 3, 6, and 12 months. Tremor assessments were videotaped and rated by an independent group of neurologists who were unaware of the treatment assignments. The primary outcome was the between-group difference in the change from baseline to 3 months in hand tremor, rated on a 32-point scale (with higher scores indicating more severe tremor). After 3 months, patients in the sham-procedure group could cross over to active treatment (the open-label extension cohort).Seventy-six patients were included in the analysis. Hand-tremor scores improved more after focused ultrasound thalamotomy (from 18.1 points at baseline to 9.6 at 3 months) than after the sham procedure (from 16.0 to 15.8 points); the between-group difference in the mean change was 8.3 points (95% confidence interval [CI], 5.9 to 10.7; P<0.001). The improvement in the thalamotomy group was maintained at 12 months (change from baseline, 7.2 points; 95% CI, 6.1 to 8.3). Secondary outcome measures assessing disability and quality of life also improved with active treatment (the blinded thalamotomy cohort)as compared with the sham procedure (P<0.001 for both comparisons). Adverse events in the thalamotomy group included gait disturbance in 36% of patients and paresthesias or numbness in 38%; these adverse events persisted at 12 months in 9% and 14% of patients, respectively.MRI-guided focused ultrasound thalamotomy reduced hand tremor in patients with essential tremor. Side effects included sensory and gait disturbances. (Funded by InSightec and others; ClinicalTrials.gov number, NCT01827904.).

  View details for DOI 10.1056/NEJMoa1600159

  View details for PubMedID 27557301

• Correcting heat-induced chemical shift distortions in proton resonance frequency-shift thermometry. Magnetic resonance in medicine Gaur, P., Partanen, A., Werner, B., Ghanouni, P., Bitton, R., Butts Pauly, K., Grissom, W. A. 2016; 76 (1): 172-182

  Abstract

  To reconstruct proton resonance frequency-shift temperature maps free of chemical shift distortions.Tissue heating created by thermal therapies such as focused ultrasound surgery results in a change in proton resonance frequency that causes geometric distortions in the image and calculated temperature maps, in the same manner as other chemical shift and off-resonance distortions if left uncorrected. We propose an online-compatible algorithm to correct these distortions in 2DFT and echo-planar imaging acquisitions, which is based on a k-space signal model that accounts for proton resonance frequency change-induced phase shifts both up to and during the readout. The method was evaluated with simulations, gel phantoms, and in vivo temperature maps from brain, soft tissue tumor, and uterine fibroid focused ultrasound surgery treatments.Without chemical shift correction, peak temperature and thermal dose measurements were spatially offset by approximately 1 mm in vivo. Spatial shifts increased as readout bandwidth decreased, as shown by up to 4-fold greater temperature hot spot asymmetry in uncorrected temperature maps. In most cases, the computation times to correct maps at peak heat were less than 10 ms, without parallelization.Heat-induced proton resonance frequency changes create chemical shift distortions in temperature maps resulting from MR-guided focused ultrasound surgery ablations, but the distortions can be corrected using an online-compatible algorithm. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.

  View details for DOI 10.1002/mrm.25899

  View details for PubMedID 26301458

  View details for PubMedCentralID PMC4766074

• Correcting Heat-Induced Chemical Shift Distortions in Proton Resonance Frequency-Shift Thermometry MAGNETIC RESONANCE IN MEDICINE Gaur, P., Partanen, A., Werner, B., Ghanouni, P., Bitton, R., Pauly, K. B., Grissom, W. A. 2016; 76 (1): 172-182

  Abstract

  To reconstruct proton resonance frequency-shift temperature maps free of chemical shift distortions.Tissue heating created by thermal therapies such as focused ultrasound surgery results in a change in proton resonance frequency that causes geometric distortions in the image and calculated temperature maps, in the same manner as other chemical shift and off-resonance distortions if left uncorrected. We propose an online-compatible algorithm to correct these distortions in 2DFT and echo-planar imaging acquisitions, which is based on a k-space signal model that accounts for proton resonance frequency change-induced phase shifts both up to and during the readout. The method was evaluated with simulations, gel phantoms, and in vivo temperature maps from brain, soft tissue tumor, and uterine fibroid focused ultrasound surgery treatments.Without chemical shift correction, peak temperature and thermal dose measurements were spatially offset by approximately 1 mm in vivo. Spatial shifts increased as readout bandwidth decreased, as shown by up to 4-fold greater temperature hot spot asymmetry in uncorrected temperature maps. In most cases, the computation times to correct maps at peak heat were less than 10 ms, without parallelization.Heat-induced proton resonance frequency changes create chemical shift distortions in temperature maps resulting from MR-guided focused ultrasound surgery ablations, but the distortions can be corrected using an online-compatible algorithm. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.

  View details for DOI 10.1002/mrm.25899

  View details for Web of Science ID 000384996900016

  View details for PubMedCentralID PMC4766074

• FREQUENCY DEPENDENCE OF ULTRASOUND NEUROSTIMULATION IN THE MOUSE BRAIN ULTRASOUND IN MEDICINE AND BIOLOGY Ye, P. P., Brown, J. R., Pauly, K. B. 2016; 42 (7): 1512-1530

  Abstract

  Ultrasound neuromodulation holds promise as a non-invasive technique for neuromodulation of the central nervous system. However, much remains to be determined about how the technique can be transformed into a useful technology, including the effect of ultrasound frequency. Previous studies have demonstrated neuromodulation in vivo using frequencies <1 MHz, with a trend toward improved efficacy with lower frequency. However, using higher frequencies could offer improved ultrasound spatial resolution. We investigate the ultrasound neuromodulation effects in mice at various frequencies both below and above 1 MHz. We find that frequencies up to 2.9 MHz can still be effective for generating motor responses, but we also confirm that as frequency increases, sonications require significantly more intensity to achieve equivalent efficacy. We argue that our results provide evidence that favors either a particle displacement or a cavitation-based mechanism for the phenomenon of ultrasound neuromodulation.

  View details for DOI 10.1016/j.ultrasmedbio.2016.02.012

  View details for Web of Science ID 000377305500011

  View details for PubMedID 27090861

  View details for PubMedCentralID PMC4899295

• Endoluminal ultrasound applicators for MR-guided thermal ablation of pancreatic tumors: Preliminary design and evaluation in a porcine pancreas model MEDICAL PHYSICS Adams, M. S., Salgaonkar, V. A., Plata-Camargo, J., Jones, P. D., Pascal-Tenorio, A., Chen, H., Bouley, D. M., Sommer, G., Pauly, K. B., Diederich, C. J. 2016; 43 (7): 4184-4197

  Abstract

  Endoluminal ultrasound may serve as a minimally invasive option for delivering thermal ablation to pancreatic tumors adjacent to the stomach or duodenum. The objective of this study was to explore the basic feasibility of this treatment strategy through the design, characterization, and evaluation of proof-of-concept endoluminal ultrasound applicators capable of placement in the gastrointestinal (GI) lumen for volumetric pancreas ablation under MR guidance.Two variants of the endoluminal applicator, each containing a distinct array of two independently powered transducers (10 × 10 mm 3.2 MHz planar; or 8 × 10 × 20 mm radius of curvature 3.3 MHz curvilinear geometries) at the distal end of a meter long flexible catheter assembly, were designed and fabricated. Transducers and circulatory water flow for acoustic coupling and luminal cooling were contained by a low-profile polyester balloon covering the transducer assembly fixture. Each applicator incorporated miniature spiral MR coils and mechanical features (guiding tips and hinges) to facilitate tracking and insertion through the GI tract under MRI guidance. Acoustic characterization of each device was performed using radiation force balance and hydrophone measurements. Device delivery into the upper GI tract, adjacent to the pancreas, and heating characteristics for treatment of pancreatic tissue were evaluated in MR-guided ex vivo and in vivo porcine experiments. MR guidance was utilized for anatomical target identification, tracking/positioning of the applicator, and MR temperature imaging (MRTI) for PRF-based multislice thermometry, implemented in the real-time RTHawk software environment.Force balance and hydrophone measurements indicated efficiencies of 48.8% and 47.8% and -3 dB intensity beam-widths of 3.2 and 1.2 mm for the planar and curvilinear transducers, respectively. Ex vivo studies on whole-porcine carcasses revealed capabilities of producing ablative temperature rise (ΔT > 15 °C) contours in pancreatic tissue 4-40 mm long and 4-28 mm wide for the planar transducer applicator (1-13 min sonication duration, ∼4 W/cm(2) applied acoustic intensity). Curvilinear transducers produced more selective heating, with a narrower ΔT > 15 °C contour length and width of up to 1-24 mm and 2-7 mm, respectively (1-7 min sonication duration, ∼4 W/cm(2) applied acoustic intensity). Active tracking of the miniature spiral coils was achieved using a Hadamard encoding tracking sequence, enabling real-time determination of each coil's coordinates and automated prescription of imaging planes for thermometry. In vivo MRTI-guided heating trials in three pigs demonstrated capability of ∼20 °C temperature elevation in pancreatic tissue at 2 cm depths from the applicator, with 5-7 W/cm(2) applied intensity and 6-16 min sonication duration. Dimensions of thermal lesions in the pancreas ranged from 12 to 28 mm, 3 to 10 mm, and 5 to 10 mm in length, width, and depth, respectively, as verified through histological analysis of tissue sections. Multiple-baseline reconstruction and respiratory-gated acquisition were demonstrated to be effective strategies in suppressing motion artifacts for clear evolution of temperature profiles during MRTI in the in vivo studies.This study demonstrates the technical feasibility of generating volumetric ablation in pancreatic tissue using endoluminal ultrasound applicators positioned in the stomach lumen. MR guidance facilitates target identification, device tracking/positioning, and treatment monitoring through real-time multislice PRF-based thermometry.

  View details for DOI 10.1118/1.4953632

  View details for Web of Science ID 000379171900027

  View details for PubMedID 27370138

  View details for PubMedCentralID PMC4912561

• Magnetic resonance-guided focused ultrasound treatment of extra-abdominal desmoid tumors: a retrospective multicenter study. European radiology Ghanouni, P., Dobrotwir, A., Bazzocchi, A., Bucknor, M., Bitton, R., Rosenberg, J., Telischak, K., Busacca, M., Ferrari, S., Albisinni, U., Walters, S., Gold, G., Ganjoo, K., Napoli, A., Pauly, K. B., Avedian, R. 2016: -?

  Abstract

  To assess the feasibility, safety and preliminary efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of extra-abdominal desmoid tumours.Fifteen patients with desmoid fibromatosis (six males, nine females; age range, 7-66 years) were treated with MRgFUS, with seven patients requiring multiple treatments (25 total treatments). Changes in viable and total tumour volumes were measured after treatment. Efficacy was evaluated using an exact one-sided Wilcoxon test to determine if the median reduction in viable tumour measured immediately after initial treatment exceeded a threshold of 50 % of the targeted volume. Median decrease after treatment of at least two points in numerical rating scale (NRS) worst and average pain scores was tested with an exact one-sided Wilcoxon test. Adverse events were recorded.After initial MRgFUS treatment, median viable targeted tumour volume decreased 63 %, significantly beyond our efficacy threshold (P = 0.0013). Median viable total tumour volume decreased (105 mL [interquartile range {IQR}, 217 mL] to 54 mL [IQR, 92 mL]) and pain improved (worst scores, 7.5 ± 1.9 vs 2.7 ± 2.6, P = 0.027; average scores, 6 ± 2.3 vs 1.3 ± 2, P = 0.021). Skin burn was the most common complication.MRgFUS significantly and durably reduced viable tumour volume and pain in this series of 15 patients with extra-abdominal desmoid fibromatosis.• Retrospective four-centre study shows MRgFUS safely and effectively treats extra-abdominal desmoid tumours • This non-invasive procedure can eradicate viable tumour in some cases • Alternatively, MRgFUS can provide durable control of tumour growth through repeated treatments • Compared to surgery or radiation, MRgFUS has relatively mild side effects.

  View details for PubMedID 27147222

• MR thermometry near metallic devices using multispectral imaging. Magnetic resonance in medicine Weber, H., Taviani, V., Yoon, D., Ghanouni, P., Pauly, K. B., Hargreaves, B. A. 2016

  Abstract

  The lack of a technique for MR thermometry near metal excludes a growing patient population from promising treatments such as MR-guided focused ultrasound therapy. Here we explore the feasibility of multispectral imaging (MSI) for noninvasive temperature measurement in the presence of strong field inhomogeneities by exploiting the temperature dependency of the T1 relaxation time.A two-dimensional inversion-recovery-prepared MSI pulse sequence (2DMSI) was implemented for artifact-reduced T1 mapping near metal. A series of T1 maps was acquired in a metallic implant phantom while increasing the phantom temperature. The measured change in T1 was analyzed with respect to the phantom temperature. For comparison, proton resonance frequency shift (PRFS) thermometry was performed.2DMSI achieved artifact-reduced, single-slice T1 mapping in the presence of strong off-resonance with a spatial resolution of 1.9 mm in-plane and a temporal resolution of 5 min. The maps enabled temperature measurements over a range of 30°C with an uncertainty below 1.4°C. The quality of the resulting temperature maps was independent of the distance from the metal, whereas the PRFS-based temperature measurements were increasingly impaired with increasing off-resonance.We demonstrated the ability to noninvasively measure temperature near metal using MSI and the T1 temperature sensitivity. Magn Reson Med, 2016. © 2016 Wiley Periodicals, Inc.

  View details for DOI 10.1002/mrm.26203

  View details for PubMedID 26991803

• Improved cortical bone specificity in UTE MR Imaging. Magnetic resonance in medicine Johnson, E. M., Vyas, U., Ghanouni, P., Pauly, K. B., Pauly, J. M. 2016

  Abstract

  Methods for direct visualization of compact bone using MRI have application in several "MR-informed" technologies, such as MR-guided focused ultrasound, MR-PET reconstruction and MR-guided radiation therapy. The specificity of bone imaging can be improved by manipulating image sensitivity to Bloch relaxation phenomena, facilitating distinction of bone from other tissues detected by MRI.From Bloch equation dynamics, excitation pulses suitable for creating specific sensitivity to short-T2 magnetization from cortical bone are identified. These pulses are used with UTE subtraction demonstrate feasibility of MR imaging of compact bone with positive contrast.MR images of bone structures are acquired with contrast similar to that observed in x-ray CT images. Through comparison of MR signal intensities with CT Hounsfield units of the skull, the similarity of contrast is quantified. The MR technique is also demonstrated in other regions of the body that are relevant for interventional procedures, such as the shoulder, pelvis and leg.Matching RF excitation pulses to relaxation rates improves the specificity to bone of short-T2 contrast. It is demonstrated with a UTE sequence to acquire images of cortical bone with positive contrast, and the contrast is verified by comparison with x-ray CT. Magn Reson Med, 2016. © 2016 Wiley Periodicals, Inc.

  View details for DOI 10.1002/mrm.26160

  View details for PubMedID 26972442

  View details for PubMedCentralID PMC5040625

• Is MR-guided High-intensity Focused Ultrasound a Feasible Treatment Modality for Desmoid Tumors? CLINICAL ORTHOPAEDICS AND RELATED RESEARCH Avedian, R. S., Bitton, R., Gold, G., Butts-Pauly, K., Ghanouni, P. 2016; 474 (3): 697-704

  Abstract

  MR-guided high-intensity focused ultrasound is a noninvasive treatment modality that uses focused ultrasound waves to thermally ablate tumors within the human body while minimizing side effects to surrounding healthy tissues. This technology is FDA-approved for certain tumors and has potential to be a noninvasive treatment option for extremity soft tissue tumors. Development of treatment modalities that achieve tumor control, decrease morbidity, or both might be of great benefit for patients. We wanted to assess the potential use of this technology in the treatment of extremity desmoid tumors.(1) Can we use MR-guided high-intensity focused ultrasound to accurately ablate a predetermined target volume within a human cadaver extremity? (2) Does MR-guided high-intensity focused ultrasound treatment stop progression and/or cause regression of extremity desmoid tumors?Simulated tumor volumes in four human cadavers, created by using plastic markers, were ablated using a commercially available focused ultrasound system. Accuracy was determined in accordance with the International Organization of Standards location error by measuring the farthest distance between the ablated tissue and the plane corresponding to the target. Between 2012 and 2014, we treated nine patients with desmoid tumors using focused ultrasound ablation. Indications for this were tumor-related symptoms or failure of conventional treatment. Of those, five of them were available for MRI followup at 12 months or longer (mean, 18.2 months; range, 12-23 months). The radiographic and clinical outcomes of five patients who had desmoid tumors treated with focused ultrasound were prospectively recorded. Patients were assessed preoperatively with MRI and followed at routine intervals after treatment with MRI scans and clinical examination.The ablation accuracy for the four cadaver extremities was 5 mm, 3 mm, 8 mm, and 8 mm. Four patients' tumors became smaller after treatment and one patient has slight progression at the time of last followup. The mean decrease in tumor size determined by MRI measurements was 36% (95% confidence interval, 7%-66%). No patient has received additional adjuvant systemic or local treatment. Treatment-related adverse events included first- and second-degree skin burns occurring in four patients, which were managed successfully without further surgery.This preliminary investigation provides some evidence that MR-guided high-intensity focused ultrasound may be a feasible treatment for desmoid tumors. It may also be of use for other soft tissue neoplasms in situations in which there are limited traditional treatment options such as recurrent sarcomas. Further investigation is necessary to better define the indications, efficacy, role, and long-term oncologic outcomes of focused ultrasound treatment.Level IV, therapeutic study.

  View details for DOI 10.1007/s11999-015-4364-0

  View details for Web of Science ID 000370150000018

  View details for PubMedID 26040967

  View details for PubMedCentralID PMC4746191

• Improving thermal dose accuracy in magnetic resonance-guided focused ultrasound surgery: Long-term thermometry using a prior baseline as a reference. Journal of magnetic resonance imaging Bitton, R. R., Webb, T. D., Pauly, K. B., Ghanouni, P. 2016; 43 (1): 181-189

  Abstract

  To investigate thermal dose volume (TDV) and non-perfused volume (NPV) of magnetic resonance-guided focused ultrasound (MRgFUS) treatments in patients with soft tissue tumors, and describe a method for MR thermal dosimetry using a baseline reference.Agreement between TDV and immediate post treatment NPV was evaluated from MRgFUS treatments of five patients with biopsy-proven desmoid tumors. Thermometry data (gradient echo, 3T) were analyzed over the entire course of the treatments to discern temperature errors in the standard approach. The technique searches previously acquired baseline images for a match using 2D normalized cross-correlation and a weighted mean of phase difference images. Thermal dose maps and TDVs were recalculated using the matched baseline and compared to NPV.TDV and NPV showed between 47%-91% disagreement, using the standard immediate baseline method for calculating TDV. Long-term thermometry showed a nonlinear local temperature accrual, where peak additional temperature varied between 4-13°C (mean = 7.8°C) across patients. The prior baseline method could be implemented by finding a previously acquired matching baseline 61% ± 8% (mean ± SD) of the time. We found 7%-42% of the disagreement between TDV and NPV was due to errors in thermometry caused by heat accrual. For all patients, the prior baseline method increased the estimated treatment volume and reduced the discrepancies between TDV and NPV (P = 0.023).This study presents a mismatch between in-treatment and post treatment efficacy measures. The prior baseline approach accounts for local heating and improves the accuracy of thermal dose-predicted volume. J. MAGN. RESON. IMAGING 2016;43:181-189.

  View details for DOI 10.1002/jmri.24978

  View details for PubMedID 26119129

  View details for PubMedCentralID PMC4691444

• A feasibility study on monitoring the evolution of apparent diffusion coefficient decrease during thermal ablation MEDICAL PHYSICS Plata, J. C., Holbrook, A. B., Marx, M., Salgaonkar, V., Jones, P., Pascal-Tenorio, A., Bouley, D., Diederich, C., Sommer, G., Pauly, K. B. 2015; 42 (9): 5130-5137

  Abstract

  Evaluate whether a decrease in apparent diffusion coefficient (ADC), associated with loss of tissue viability (LOTV), can be observed during the course of thermal ablation of the prostate.Thermal ablation was performed in a healthy in vivo canine prostate model (N = 2, ages: 5 yr healthy, mixed breed, weights: 13-14 kg) using a transurethral high-intensity ultrasound catheter and was monitored using a strategy that interleaves diffusion weighted images and gradient-echo images. The two sequences were used to measure ADC and changes in temperature during the treatment. Changes in temperature were used to compute expected changes in ADC. The difference between expected and measured ADC, ADCDIFF, was analyzed in regions ranging from moderate hyperthermia to heat fixation. A receiver operator characteristic (ROC) curve analysis was used to select a threshold of detection of LOTV. Time of threshold activation, tLOTV, was compared with time to reach CEM43 = 240, tDOSE.The observed relationship between temperature and ADC in vivo (2.2%/ °C, 1.94%-2.47%/ °C 95% confidence interval) was not significantly different than the previously reported value of 2.4%/ °C in phantom. ADCDIFF changes after correction for temperature showed a mean decrease of 25% in ADC 60 min post-treatment in regions where sufficient thermal dose (CEM43 > 240) was achieved. Following our ROC analysis, a threshold of 2.25% decrease in ADCDIFF for three consecutive time points was chosen as an indicator of LOTV. The ADCDIFF was found to decrease quickly (1-2 min) after reaching CEM43 = 240 in regions associated with heat fixation and more slowly (10-20 min) in regions that received slower heating.Simultaneous monitoring of ADC and temperature during treatment might allow for a more complete tissue viability assessment of ablative thermal treatments in the prostate. ADCDIFF decreases during the course of treatment may be interpreted as loss of tissue viability.

  View details for DOI 10.1118/1.4928155

  View details for Web of Science ID 000360645000015

  View details for PubMedCentralID PMC4537482

• A feasibility study on monitoring the evolution of apparent diffusion coefficient decrease during thermal ablation. Medical physics Plata, J. C., Holbrook, A. B., Marx, M., Salgaonkar, V., Jones, P., Pascal-Tenorio, A., Bouley, D., Diederich, C., Sommer, G., Pauly, K. B. 2015; 42 (9): 5130-5137

  Abstract

  Evaluate whether a decrease in apparent diffusion coefficient (ADC), associated with loss of tissue viability (LOTV), can be observed during the course of thermal ablation of the prostate.Thermal ablation was performed in a healthy in vivo canine prostate model (N = 2, ages: 5 yr healthy, mixed breed, weights: 13-14 kg) using a transurethral high-intensity ultrasound catheter and was monitored using a strategy that interleaves diffusion weighted images and gradient-echo images. The two sequences were used to measure ADC and changes in temperature during the treatment. Changes in temperature were used to compute expected changes in ADC. The difference between expected and measured ADC, ADCDIFF, was analyzed in regions ranging from moderate hyperthermia to heat fixation. A receiver operator characteristic (ROC) curve analysis was used to select a threshold of detection of LOTV. Time of threshold activation, tLOTV, was compared with time to reach CEM43 = 240, tDOSE.The observed relationship between temperature and ADC in vivo (2.2%/ °C, 1.94%-2.47%/ °C 95% confidence interval) was not significantly different than the previously reported value of 2.4%/ °C in phantom. ADCDIFF changes after correction for temperature showed a mean decrease of 25% in ADC 60 min post-treatment in regions where sufficient thermal dose (CEM43 > 240) was achieved. Following our ROC analysis, a threshold of 2.25% decrease in ADCDIFF for three consecutive time points was chosen as an indicator of LOTV. The ADCDIFF was found to decrease quickly (1-2 min) after reaching CEM43 = 240 in regions associated with heat fixation and more slowly (10-20 min) in regions that received slower heating.Simultaneous monitoring of ADC and temperature during treatment might allow for a more complete tissue viability assessment of ablative thermal treatments in the prostate. ADCDIFF decreases during the course of treatment may be interpreted as loss of tissue viability.

  View details for DOI 10.1118/1.4928155

  View details for PubMedID 26328964

• Toward Volumetric MR Thermometry With the MASTER Sequence IEEE TRANSACTIONS ON MEDICAL IMAGING Marx, M., Plata, J., Pauly, K. B. 2015; 34 (1): 148-155

  Abstract

  MR temperature monitoring is an indispensable tool for high intensity focused ultrasound. In this paper, a new technique known as MASTER (multiple adjacent slice thermometry with excitation refocusing) is presented which improves the speed and accuracy of multiple-slice MR thermometry. Defocusing the magnetization after exciting a slice allows for multiple slices to be excited concurrently and stored in k-space. The magnetization from each excitation is then refocused and read in sequence. This approach increases TE for each slice, greatly improving temperature SNR as compared to conventional slice interleaving. Gradient sequence design optimization is required to minimize diffusion losses while maintaining high sequence efficiency. Flexibility in selecting position, update rate, accuracy, and voxel size for each slice independently allows for freedom in design to fit different application needs. Results are shown in phantom and in vivo validating the feasibility of the sequence, and comparing it to interleaved GRE. Sample design curves are presented that contrast the MASTER design space with that of interleaved GRE thermometry.

  View details for DOI 10.1109/TMI.2014.2349912

  View details for Web of Science ID 000346975900015

  View details for PubMedID 25163055

  View details for PubMedCentralID PMC4280319

• Dual-Mode Integrated Circuit for Imaging and HIFU With 2-D CMUT Arrays Jang, J., Rasmussen, M., Bhuyan, A., Yoon, H., Moini, A., Chang, C., Watkins, R. D., Choe, J., Nikoozadeh, A., Stephens, D., Oralkan, O., Pauly, K., Khuri-Yakub, B., IEEE IEEE. 2015

  View details for DOI 10.1109/ULTSYM.2015.0166

  View details for Web of Science ID 000366045700087

• Autonomous Real-Time Interventional Scan Plane Control With a 3-D Shape-Sensing Needle IEEE TRANSACTIONS ON MEDICAL IMAGING Elayaperumal, S., Plata, J. C., Holbrook, A. B., Park, Y., Pauly, K. B., Daniel, B. L., Cutkosky, M. R. 2014; 33 (11): 2128-2139

  Abstract

  This study demonstrates real-time scan plane control dependent on three-dimensional needle bending, as measured from magnetic resonance imaging (MRI)-compatible optical strain sensors. A biopsy needle with embedded fiber Bragg grating (FBG) sensors to measure surface strains is used to estimate its full 3-D shape and control the imaging plane of an MR scanner in real-time, based on the needle's estimated profile. The needle and scanner coordinate frames are registered to each other via miniature radio-frequency (RF) tracking coils, and the scan planes autonomously track the needle as it is deflected, keeping its tip in view. A 3-D needle annotation is superimposed over MR-images presented in a 3-D environment with the scanner's frame of reference. Scan planes calculated based on the FBG sensors successfully follow the tip of the needle. Experiments using the FBG sensors and RF coils to track the needle shape and location in real-time had an average root mean square error of 4.2 mm when comparing the estimated shape to the needle profile as seen in high resolution MR images. This positional variance is less than the image artifact caused by the needle in high resolution SPGR (spoiled gradient recalled) images. Optical fiber strain sensors can estimate a needle's profile in real-time and be used for MRI scan plane control to potentially enable faster and more accurate physician response.

  View details for DOI 10.1109/TMI.2014.2332354

  View details for Web of Science ID 000344589200006

  View details for PubMedID 24968093

• Localization of ultrasound-induced in vivo neurostimulation in the mouse model. Ultrasound in medicine and biology King, R. L., Brown, J. R., Pauly, K. B. 2014; 40 (7): 1512-1522

  Abstract

  Developments in the use of ultrasound to stimulate and modulate neural activity have raised the possibility of using ultrasound as a new investigative and therapeutic tool in brain research. Although the phenomenon of ultrasound-induced neurostimulation has a long history dating back many decades, until now there has been little evidence of a clearly localized effect in the brain, a necessary requirement for the technique to become genuinely useful. Here we report clearly distinguishable effects in sonicating rostral and caudal regions of the mouse motor cortex. Motor responses measured by normalized electromyography in the neck and tail regions changed significantly when sonicating the two different areas of motor cortex. Response latencies varied significantly according to sonication location, suggesting that different neural circuits are activated depending on the precise focus of the ultrasound beam. Taken together, our findings present good evidence of the ability to target selective parts of the motor cortex with ultrasound neurostimulation in the mouse, an advance that should help to set the stage for developing new applications in larger animal models, including humans.

  View details for DOI 10.1016/j.ultrasmedbio.2014.01.020

  View details for PubMedID 24642220

• MR-acoustic radiation force imaging (MR-ARFI) and susceptibility weighted imaging (SWI) to visualize calcifications in ex vivo swine brain. Journal of magnetic resonance imaging Bitton, R. R., Pauly, K. R. 2014; 39 (5): 1294-1300

  Abstract

  To present the use of MR-acoustic radiation force imaging (MR-ARFI) and susceptibility weighted imaging (SWI) to visualize calcifications in ex vivo brain tissue as a planning indicator for MR-guided focused ultrasound (MRgFUS).Calcifications were implanted in ex vivo swine brain and imaged using SWI, MR-ARFI, and computed tomography (CT). SWI-filtered phase images used 3D gradient recalled echo (GRE) images with a Fourier-based unwrapping algorithm. The MR-ARFI pulse sequence used a 2DFT spin-echo with repeated bipolar encoding gradients in the direction of the longitudinal ultrasound beam. MR-ARFI interrogations scanned a subregion (14 × 10 × 12 mm) of the brain surrounding the calcification. They were combined into a single displacement weighted map, using the sum of squares method. Calcification size estimates were based on image profiles plotted along the ±x and ±z direction, at the full-width half-maximum.Both MR-ARFI and SWI were able to visualize the calcifications. The contrast ratio was 150 for CT, 12 for SWI, and 12 for MR-ARFI. Profile measures were 1.35 × 1.28 mm on CT, 1.24 × 1.73 mm on SWI, and 2.45 × 3.02 mm on MR-ARFI. MR-ARFI displacement showed a linear increase with acoustic power (20-80W), and also increased with calcification size.The use of SWI-filtered phase and MR-ARFI have the potential to provide a clinical indicator of calcification relevance in the planning of a transcranial MRgFUS treatment.J. Magn. Reson. Imaging 2013. © 2013 Wiley Periodicals, Inc.

  View details for DOI 10.1002/jmri.24255

  View details for PubMedID 24123504

• Transcranial phase aberration correction using beam simulations and MR-ARFI. Medical physics Vyas, U., Kaye, E., Pauly, K. B. 2014; 41 (3): 032901-?

  Abstract

  Transcranial magnetic resonance-guided focused ultrasound surgery is a noninvasive technique for causing selective tissue necrosis. Variations in density, thickness, and shape of the skull cause aberrations in the location and shape of the focal zone. In this paper, the authors propose a hybrid simulation-MR-ARFI technique to achieve aberration correction for transcranial MR-guided focused ultrasound surgery. The technique uses ultrasound beam propagation simulations with MR Acoustic Radiation Force Imaging (MR-ARFI) to correct skull-caused phase aberrations.Skull-based numerical aberrations were obtained from a MR-guided focused ultrasound patient treatment and were added to all elements of the InSightec conformal bone focused ultrasound surgery transducer during transmission. In the first experiment, the 1024 aberrations derived from a human skull were condensed into 16 aberrations by averaging over the transducer area of 64 elements. In the second experiment, all 1024 aberrations were applied to the transducer. The aberrated MR-ARFI images were used in the hybrid simulation-MR-ARFI technique to find 16 estimated aberrations. These estimated aberrations were subtracted from the original aberrations to result in the corrected images. Each aberration experiment (16-aberration and 1024-aberration) was repeated three times.The corrected MR-ARFI image was compared to the aberrated image and the ideal image (image with zero aberrations) for each experiment. The hybrid simulation-MR-ARFI technique resulted in an average increase in focal MR-ARFI phase of 44% for the 16-aberration case and 52% for the 1024-aberration case, and recovered 83% and 39% of the ideal MR-ARFI phase for the 16-aberrations and 1024-aberration case, respectively.Using one MR-ARFI image and noa priori information about the applied phase aberrations, the hybrid simulation-MR-ARFI technique improved the maximum MR-ARFI phase of the beam's focus.

  View details for DOI 10.1118/1.4865778

  View details for PubMedID 24593740

• Voltage-Based Device Tracking in a 1.5 Tesla MRI During Imaging: Initial Validation in Swine Models MAGNETIC RESONANCE IN MEDICINE Schmidt, E. J., Tse, Z. T., Reichlin, T. R., Michaud, G. F., Watkins, R. D., Butts-Pauly, K., Kwong, R. Y., Stevenson, W., Schweitzer, J., Byrd, I., Dumoulin, C. L. 2014; 71 (3): 1197-1209

  Abstract

  Voltage-based device-tracking (VDT) systems are commonly used for tracking invasive devices in electrophysiological cardiac-arrhythmia therapy. During electrophysiological procedures, electro-anatomic mapping workstations provide guidance by integrating VDT location and intracardiac electrocardiogram information with X-ray, computerized tomography, ultrasound, and MR images. MR assists navigation, mapping, and radiofrequency ablation. Multimodality interventions require multiple patient transfers between an MRI and the X-ray/ultrasound electrophysiological suite, increasing the likelihood of patient-motion and image misregistration. An MRI-compatible VDT system may increase efficiency, as there is currently no single method to track devices both inside and outside the MRI scanner.An MRI-compatible VDT system was constructed by modifying a commercial system. Hardware was added to reduce MRI gradient-ramp and radiofrequency unblanking pulse interference. VDT patches and cables were modified to reduce heating. Five swine cardiac VDT electro-anatomic mapping interventions were performed, navigating inside and thereafter outside the MRI.Three-catheter VDT interventions were performed at >12 frames per second both inside and outside the MRI scanner with <3 mm error. Catheters were followed on VDT- and MRI-derived maps. Simultaneous VDT and imaging was possible in repetition time >32 ms sequences with <0.5 mm errors, and <5% MRI signal-to-noise ratio (SNR) loss. At shorter repetition times, only intracardiac electrocardiogram was reliable. Radiofrequency heating was <1.5°C.An MRI-compatible VDT system is feasible.

  View details for DOI 10.1002/mrm.24742

  View details for Web of Science ID 000331614600035

  View details for PubMedID 23580479

  View details for PubMedCentralID PMC3884036

• Respiration based steering for high intensity focused ultrasound liver ablation. Magnetic resonance in medicine Holbrook, A. B., Ghanouni, P., Santos, J. M., Dumoulin, C., Medan, Y., Pauly, K. B. 2014; 71 (2): 797-806

  Abstract

  PURPOSE: Respiratory motion makes hepatic ablation using high intensity focused ultrasound (HIFO) challenging. Previous HIFU liver treatment had required apnea induced during general anesthesia. We describe and test a system that allows treatment of the liver in the presence of breathing motion. METHODS: Mapping a signal from an external respiratory bellow to treatment locations within the liver allows the ultrasound transducer to be steered in real time to the target location. Using a moving phantom, three metrics were used to compare static, steered, and unsteered sonications: the area of sonications once a temperature rise of 15°C was achieved, the energy deposition required to reach that temperature, and the average rate of temperature rise during the first 10 s of sonication. Steered HIFU in vivo ablations of the porcine liver were also performed and compared to breath-hold ablations. RESULTS: For the last phantom metric, all groups were found to be statistically significantly different (P ≤ 0.003). However, in the other two metrics, the static and unsteered sonications were not statistically different (P > 0.9999). Steered in vivo HIFU ablations were not statistically significantly different from ablations during breath-holding. CONCLUSIONS: A system for performing HIFU steering during ablation of the liver with breathing motion is presented and shown to achieve results equivalent to ablation performed with breath-holding. Magn Reson Med 000:000-000, 2012. © 2012 Wiley Periodicals, Inc.

  View details for DOI 10.1002/mrm.24695

  View details for PubMedID 23460510

• Respiration Based Steering for High Intensity Focused Ultrasound Liver Ablation MAGNETIC RESONANCE IN MEDICINE Holbrook, A. B., Ghanouni, P., Santos, J. M., Dumoulin, C., Medan, Y., Pauly, K. B. 2014; 71 (2): 797-806

  Abstract

  PURPOSE: Respiratory motion makes hepatic ablation using high intensity focused ultrasound (HIFO) challenging. Previous HIFU liver treatment had required apnea induced during general anesthesia. We describe and test a system that allows treatment of the liver in the presence of breathing motion. METHODS: Mapping a signal from an external respiratory bellow to treatment locations within the liver allows the ultrasound transducer to be steered in real time to the target location. Using a moving phantom, three metrics were used to compare static, steered, and unsteered sonications: the area of sonications once a temperature rise of 15°C was achieved, the energy deposition required to reach that temperature, and the average rate of temperature rise during the first 10 s of sonication. Steered HIFU in vivo ablations of the porcine liver were also performed and compared to breath-hold ablations. RESULTS: For the last phantom metric, all groups were found to be statistically significantly different (P ≤ 0.003). However, in the other two metrics, the static and unsteered sonications were not statistically different (P > 0.9999). Steered in vivo HIFU ablations were not statistically significantly different from ablations during breath-holding. CONCLUSIONS: A system for performing HIFU steering during ablation of the liver with breathing motion is presented and shown to achieve results equivalent to ablation performed with breath-holding. Magn Reson Med 000:000-000, 2012. © 2012 Wiley Periodicals, Inc.

  View details for DOI 10.1002/mrm.24695

  View details for Web of Science ID 000330769700036

• Investigating the Feasibility of Rapid MRI for Image-Guided Motion Management in Lung Cancer Radiotherapy BIOMED RESEARCH INTERNATIONAL Sawant, A., Keall, P., Pauly, K. B., Alley, M., Vasanawala, S., Loo, B. W., Hinkle, J., Joshi, S. 2014

  Abstract

  Cycle-to-cycle variations in respiratory motion can cause significant geometric and dosimetric errors in the administration of lung cancer radiation therapy. A common limitation of the current strategies for motion management is that they assume a constant, reproducible respiratory cycle. In this work, we investigate the feasibility of using rapid MRI for providing long-term imaging of the thorax in order to better capture cycle-to-cycle variations. Two nonsmall-cell lung cancer patients were imaged (free-breathing, no extrinsic contrast, and 1.5 T scanner). A balanced steady-state-free-precession (b-SSFP) sequence was used to acquire cine-2D and cine-3D (4D) images. In the case of Patient 1 (right midlobe lesion, ~40 mm diameter), tumor motion was well correlated with diaphragmatic motion. In the case of Patient 2, (left upper-lobe lesion, ~60 mm diameter), tumor motion was poorly correlated with diaphragmatic motion. Furthermore, the motion of the tumor centroid was poorly correlated with the motion of individual points on the tumor boundary, indicating significant rotation and/or deformation. These studies indicate that image quality and acquisition speed of cine-2D MRI were adequate for motion monitoring. However, significant improvements are required to achieve comparable speeds for truly 4D MRI. Despite several challenges, rapid MRI offers a feasible and attractive tool for noninvasive, long-term motion monitoring.

  View details for DOI 10.1155/2014/485067

  View details for Web of Science ID 000330472600001

  View details for PubMedID 24524077

  View details for PubMedCentralID PMC3913339

• Quantifying the local tissue volume and composition in individual brains with magnetic resonance imaging NATURE MEDICINE Mezer, A., Yeatman, J. D., Stikov, N., Kay, K. N., Cho, N., Dougherty, R. F., Perry, M. L., Parvizi, J., Hua, L. H., Butts-Pauly, K., Wandell, B. A. 2013; 19 (12): 1667-1672

  Abstract

  Here, we describe a quantitative neuroimaging method to estimate the macromolecular tissue volume (MTV), a fundamental measure of brain anatomy. By making measurements over a range of field strengths and scan parameters, we tested the key assumptions and the robustness of the method. The measurements confirm that a consistent quantitative estimate of MTV can be obtained across a range of scanners. MTV estimates are sufficiently precise to enable a comparison between data obtained from an individual subject with control population data. We describe two applications. First, we show that MTV estimates can be combined with T1 and diffusion measurements to augment our understanding of the tissue properties. Second, we show that MTV provides a sensitive measure of disease status in individual patients with multiple sclerosis. The MTV maps are obtained using short clinically appropriate scans that can reveal how tissue changes influence behavior and cognition.

  View details for DOI 10.1038/nm.3390

  View details for Web of Science ID 000328181400038

  View details for PubMedID 24185694

  View details for PubMedCentralID PMC3855886

• Comparison of Temperature Processing Methods for Monitoring Focused Ultrasound Ablation in the Brain JOURNAL OF MAGNETIC RESONANCE IMAGING Rieke, V., Instrella, R., Rosenberg, J., Grissom, W., Werner, B., Martin, E., Pauly, K. B. 2013; 38 (6): 1462-1471

  Abstract

  To investigate the performance of different reconstruction methods for monitoring temperature changes during transcranial magnetic resonance imaging (MRI)-guided focused ultrasound (MRgFUS).Four different temperature reconstruction methods were compared in volunteers (without heating) and patients undergoing transcranial MRgFUS: single baseline subtraction, multibaseline subtraction, hybrid single baseline/referenceless reconstruction, and hybrid multibaseline/referenceless reconstruction. Absolute temperature error and temporal temperature uncertainty of the different reconstruction methods were analyzed and compared.Absolute temperature errors and temporal temperature uncertainty were highest with single baseline subtraction and lowest with hybrid multibaseline/referenceless reconstruction in all areas of the brain. Pulsation of the brain and susceptibility changes from tongue motion or swallowing caused substantial temperature errors when single or multibaseline subtraction was used, which were much reduced when the referenceless component was added to the reconstruction.Hybrid multibaseline/referenceless thermometry accurately measures temperature changes in the brain with fewer artifacts and errors due to motion than pure baseline subtraction methods.

  View details for DOI 10.1002/jmri.24117

  View details for Web of Science ID 000327756800019

  View details for PubMedID 23559437

  View details for PubMedCentralID PMC3775924

• Improved sleep MRI at 3 tesla in patients with obstructive sleep apnea. Journal of magnetic resonance imaging Shin, L. K., Holbrook, A. B., Capasso, R., Kushida, C. A., Powell, N. B., Fischbein, N. J., Pauly, K. B. 2013; 38 (5): 1261-1266

  Abstract

  PURPOSE: To describe a real-time MR imaging platform for synchronous, multi-planar visualization of upper airway collapse in obstructive sleep apnea at 3 Tesla (T) to promote natural sleep with an emphasis on lateral wall visualization. MATERIALS AND METHODS: A real-time imaging platform was configured for sleep MR imaging which used a cartesian, partial k-space gradient-echo sequence with an inherent temporal resolution of 3 independent slices every 2 s. Combinations of axial, mid-sagittal, and coronal scan planes were acquired. The system was tested in five subjects with polysomnography-proven obstructive sleep apnea during sleep, with synchronous acquisition of respiratory effort and combined oral-nasal airflow data. RESULTS: Sleep was initiated and maintained to allow demonstration of sleep-induced, upper airway collapse as illustrated in two subjects when using a real-time, sleep MR imaging platform at 3T. Lateral wall collapse could not be visualized on mid-sagittal imaging alone and was best characterized on multiplanar coronal and axial imaging planes. CONCLUSION: Our dedicated sleep MR imaging platform permitted an acoustic environment of constant "white noise" which was conducive to sleep onset and sleep maintenance in obstructive sleep apnea patients at 3T. Apneic episodes, specifically the lateral walls, were more accurately characterized with synchronous, multiplanar acquisitions. J. Magn. Reson. Imaging 2013;. © 2013 Wiley Periodicals, Inc.

  View details for DOI 10.1002/jmri.24029

  View details for PubMedID 23390078

• Applicators for magnetic resonance-guided ultrasonic ablation of benign prostatic hyperplasia. Investigative radiology Sommer, G., Pauly, K. B., Holbrook, A., Plata, J., Daniel, B., Bouley, D., Gill, H., Prakash, P., Salgaonkar, V., Jones, P., Diederich, C. 2013; 48 (6): 387-394

  Abstract

  The aims of this study were to evaluate in a canine model applicators designed for ablation of human benign prostatic hyperplasia (BPH) in vivo under magnetic resonance imaging (MRI) guidance, including magnetic resonance thermal imaging (MRTI), determine the ability of MRI techniques to visualize ablative changes in prostate, and evaluate the acute and longer term histologic appearances of prostate tissue ablated during these studies.An MRI-compatible transurethral device incorporating a tubular transducer array with dual 120° sectors was used to ablate canine prostate tissue in vivo, in zones similar to regions of human BPH (enlarged transition zones). Magnetic resonance thermal imaging was used for monitoring of ablation in a 3-T environment, and postablation MRIs were performed to determine the visibility of ablated regions. Three canine prostates were ablated in acute studies, and 2 animals were rescanned before killing at 31 days postablation. Acute and chronic appearances of ablated prostate tissue were evaluated histologically and were correlated with the MRTI and postablation MRI scans.It was possible to ablate regions similar in size to enlarged transition zone in human BPH in 6 to 18 minutes. Regions of acute ablation showed a central "heat-fixed" region surrounded by a region of more obvious necrosis with complete disruption of tissue architecture. After 31 days, ablated regions demonstrated complete apparent resorption of ablated tissue with formation of cystic regions containing fluid. The inherent cooling of the urethra using the technique resulted in complete urethral preservation in all cases.Prostatic ablation of zones of size and shape corresponding to human BPH is possible using appropriate transurethral applicators using MRTI, and ablated tissue may be depicted clearly in contrast-enhanced magnetic resonance images. The ability accurately to monitor prostate tissue heating, the apparent resorption of ablated regions over 1 month, and the inherent urethral preservation suggest that the magnetic resonance-guided techniques described are highly promising for the in vivo ablation of symptomatic human BPH.

  View details for DOI 10.1097/RLI.0b013e31827fe91e

  View details for PubMedID 23462673

• Focal ablation of prostate cancer: four roles for magnetic resonance imaging guidance CANADIAN JOURNAL OF UROLOGY Sommer, G., Bouley, D., Gill, H., Daniel, B., Pauly, K. B., Diederich, C. 2013; 20 (2): 6672-6681

  Abstract

  There is currently a great deal of interest in the possible use of focal therapies for prostate cancer, since such treatments offer the prospect for control or cure of the primary disease with minimal side effects. Many forms of thermal therapy have been proposed for focal ablation of prostate cancer, including laser, high intensity ultrasound and cryotherapy. This review will demonstrate the important roles that magnetic resonance imaging (MRI) guidance can offer to such focal ablation, focusing on the use of high intensity ultrasonic applicators as an example of one promising technique.Transurethral and interstitial high intensity ultrasonic applicators, designed specifically for ablation of prostate tissue were tested extensively in vivo in a canine model. The roles of MRI in positioning the devices, monitoring prostate ablation, and depicting ablated tissue were assessed using appropriate MRI sequences.MRI guidance provides a very effective tool for the positioning of ablative devices in the prostate, and thermal monitoring successfully predicted ablation of prostate tissue when a threshold of 52 ºC was achieved. Contrast enhanced MRI accurately depicted the distribution of ablated prostate tissue, which is resorbed at 30 days.Guidance of thermal therapies for focal ablation of prostate cancer will likely prove critically dependent on MRI functioning in four separate roles. Our studies indicate that in three roles: device positioning; thermal monitoring of prostate ablation; and depiction of ablated prostate tissue, MR techniques are highly accurate and likely to be of great benefit in focal prostate cancer ablation. A fourth critical role, identification of cancer within the gland for targeting of thermal therapy, is more problematic at present, but will likely become practical with further technological advances.

  View details for PubMedID 23587506

• Adapting MRI acoustic radiation force imaging for in vivo human brain focused ultrasound applications MAGNETIC RESONANCE IN MEDICINE Kaye, E. A., Pauly, K. B. 2013; 69 (3): 724-733

  Abstract

  A variety of magnetic resonance imaging acoustic radiation force imaging (MR-ARFI) pulse sequences as the means for image guidance of focused ultrasound therapy have been recently developed and tested ex vivo and in animal models. To successfully translate MR-ARFI guidance into human applications, ensuring that MR-ARFI provides satisfactory image quality in the presence of patient motion and deposits safe amount of ultrasound energy during image acquisition is necessary. The first aim of this work was to study the effect of motion on in vivo displacement images of the brain obtained with 2D Fourier transform spin echo MR-ARFI. Repeated bipolar displacement encoding configuration was shown less sensitive to organ motion. The optimal signal-to-noise ratio of displacement images was found for the duration of encoding gradients of 12 ms. The second aim was to further optimize the displacement signal-to-noise ratio for a particular tissue type by setting the time offset between the ultrasound emission and encoding based on the tissue response to acoustic radiation force. A method for measuring tissue response noninvasively was demonstrated. Finally, a new method for simultaneous monitoring of tissue heating during MR-ARFI acquisition was presented to enable timely adjustment of the ultrasound energy aimed at ensuring the safety of the MR-ARFI acquisition.

  View details for DOI 10.1002/mrm.24308

  View details for Web of Science ID 000315331300014

  View details for PubMedID 22555751

• Prospective motion correction using tracking coils MAGNETIC RESONANCE IN MEDICINE Qin, L., Schmidt, E. J., Tse, Z. T., Santos, J., Hoge, W. S., Tempany-Afdhal, C., Butts-Pauly, K., Dumoulin, C. L. 2013; 69 (3): 749-759

  Abstract

  Intracavity imaging coils provide higher signal-to-noise than surface coils and have the potential to provide higher spatial resolution in shorter acquisition times. However, images from these coils suffer from physiologically induced motion artifacts, as both the anatomy and the coils move during image acquisition. We developed prospective motion-correction techniques for intracavity imaging using an array of tracking coils. The system had <50 ms latency between tracking and imaging, so that the images from the intracavity coil were acquired in a frame of reference defined by the tracking array rather than by the system's gradient coils. Two-dimensional gradient-recalled and three-dimensional electrocardiogram-gated inversion-recovery-fast-gradient-echo sequences were tested with prospective motion correction using ex vivo hearts placed on a moving platform simulating both respiratory and cardiac motion. Human abdominal tests were subsequently conducted. The tracking array provided a positional accuracy of 0.7 ± 0.5 mm, 0.6 ± 0.4 mm, and 0.1 ± 0.1 mm along the X, Y, and Z directions at a rate of 20 frames-per-second. The ex vivo and human experiments showed significant image quality improvements for both in-plane and through-plane motion correction, which although not performed in intracavity imaging, demonstrates the feasibility of implementing such a motion-correction system in a future design of combined tracking and intracavity coil.

  View details for DOI 10.1002/mrm.24310

  View details for Web of Science ID 000315331300016

  View details for PubMedID 22565377

  View details for PubMedCentralID PMC3416927

• EFFECTIVE PARAMETERS FOR ULTRASOUND-INDUCED IN VIVO NEUROSTIMULATION ULTRASOUND IN MEDICINE AND BIOLOGY King, R. L., Brown, J. R., Newsome, W. T., Pauly, K. B. 2013; 39 (2): 312-331

  Abstract

  Ultrasound-induced neurostimulation has recently gained increasing attention, but little is known about the mechanisms by which it affects neural activity or about the range of acoustic parameters and stimulation protocols that elicit responses. We have established conditions for transcranial stimulation of the nervous system in vivo, using the mouse somatomotor response. We report that (1) continuous-wave stimuli are as effective as or more effective than pulsed stimuli in eliciting responses, and responses are elicited with stimulus onset rather than stimulus offset; (2) stimulation success increases as a function of both acoustic intensity and acoustic duration; (3) interactions of intensity and duration suggest that successful stimulation results from the integration of stimulus amplitude over a time interval of 50 to 150 ms; and (4) the motor response elicited appears to be an all-or-nothing phenomenon, meaning stronger stimulus intensities and durations increase the probability of a motor response without affecting the duration or strength of the response.

  View details for DOI 10.1016/j.ultrasmedbio.2012.09.009

  View details for Web of Science ID 000313207100015

  View details for PubMedID 23219040

• A novel approach for global noise reduction in resting-state fMRI: APPLECOR NEUROIMAGE Marx, M., Pauly, K. B., Chang, C. 2013; 64: 19-31

  Abstract

  Noise in fMRI recordings creates uncertainty when mapping functional networks in the brain. Non-neural physiological processes can introduce correlated noise across much of the brain, altering the apparent strength and extent of intrinsic networks. In this work, a new data-driven noise correction, termed "APPLECOR" (for Affine Parameterization of Physiological Large-scale Error Correction), is introduced. APPLECOR models spatially-common physiological noise as the linear combination of an additive term and a mean-dependent multiplicative term, and then estimates and removes these components. APPLECOR is shown to achieve greater consistency of the default mode network across time and across subjects than was achieved using global mean regression, respiratory volume and heart rate correction (RVHRCOR (Chang et al., 2009)), or no correction. Combining APPLECOR with RVHRCOR regressors attained greater consistency than either correction alone. Use of the proposed noise-reduction approach may help to better identify and delineate the structure of resting state networks.

  View details for DOI 10.1016/j.neuroimage.2012.09.040

  View details for Web of Science ID 000312504200003

  View details for PubMedID 23022327

  View details for PubMedCentralID PMC3508249

• The road to clinical use of high-intensity focused ultrasound for liver cancer: technical and clinical consensus. Journal of therapeutic ultrasound Aubry, J., Pauly, K. B., Moonen, C., Haar, G. t., Ries, M., Salomir, R., Sokka, S., Sekins, K. M., Shapira, Y., Ye, F., Huff-Simonin, H., Eames, M., Hananel, A., Kassell, N., Napoli, A., Hwang, J. H., Wu, F., Zhang, L., Melzer, A., Kim, Y., Gedroyc, W. M. 2013; 1: 13-?

  Abstract

  Clinical use of high-intensity focused ultrasound (HIFU) under ultrasound or MR guidance as a non-invasive method for treating tumors is rapidly increasing. Tens of thousands of patients have been treated for uterine fibroid, benign prostate hyperplasia, bone metastases, or prostate cancer. Despite the methods' clinical potential, the liver is a particularly challenging organ for HIFU treatment due to the combined effect of respiratory-induced liver motion, partial blocking by the rib cage, and high perfusion/flow. Several technical and clinical solutions have been developed by various groups during the past 15 years to compensate for these problems. A review of current unmet clinical needs is given here, as well as a consensus from a panel of experts about technical and clinical requirements for upcoming pilot and pivotal studies in order to accelerate the development and adoption of focused ultrasound for the treatment of primary and secondary liver cancer.

  View details for DOI 10.1186/2050-5736-1-13

  View details for PubMedID 25512859

• Application of Zernike polynomials towards accelerated adaptive focusing of transcranial high intensity focused ultrasound MEDICAL PHYSICS Kaye, E. A., Hertzberg, Y., Marx, M., Werner, B., Navon, G., Levoy, M., Pauly, K. B. 2012; 39 (10): 6254-6263

  Abstract

  To study the phase aberrations produced by human skulls during transcranial magnetic resonance imaging guided focused ultrasound surgery (MRgFUS), to demonstrate the potential of Zernike polynomials (ZPs) to accelerate the adaptive focusing process, and to investigate the benefits of using phase corrections obtained in previous studies to provide the initial guess for correction of a new data set.The five phase aberration data sets, analyzed here, were calculated based on preoperative computerized tomography (CT) images of the head obtained during previous transcranial MRgFUS treatments performed using a clinical prototype hemispherical transducer. The noniterative adaptive focusing algorithm [Larrat et al., "MR-guided adaptive focusing of ultrasound," IEEE Trans. Ultrason. Ferroelectr. Freq. Control 57(8), 1734-1747 (2010)] was modified by replacing Hadamard encoding with Zernike encoding. The algorithm was tested in simulations to correct the patients' phase aberrations. MR acoustic radiation force imaging (MR-ARFI) was used to visualize the effect of the phase aberration correction on the focusing of a hemispherical transducer. In addition, two methods for constructing initial phase correction estimate based on previous patient's data were investigated. The benefits of the initial estimates in the Zernike-based algorithm were analyzed by measuring their effect on the ultrasound intensity at the focus and on the number of ZP modes necessary to achieve 90% of the intensity of the nonaberrated case.Covariance of the pairs of the phase aberrations data sets showed high correlation between aberration data of several patients and suggested that subgroups can be based on level of correlation. Simulation of the Zernike-based algorithm demonstrated the overall greater correction effectiveness of the low modes of ZPs. The focal intensity achieves 90% of nonaberrated intensity using fewer than 170 modes of ZPs. The initial estimates based on using the average of the phase aberration data from the individual subgroups of subjects was shown to increase the intensity at the focal spot for the five subjects.The application of ZPs to phase aberration correction was shown to be beneficial for adaptive focusing of transcranial ultrasound. The skull-based phase aberrations were found to be well approximated by the number of ZP modes representing only a fraction of the number of elements in the hemispherical transducer. Implementing the initial phase aberration estimate together with Zernike-based algorithm can be used to improve the robustness and can potentially greatly increase the viability of MR-ARFI-based focusing for a clinical transcranial MRgFUS therapy.

  View details for DOI 10.1118/1.4752085

  View details for Web of Science ID 000310101900044

  View details for PubMedID 23039661

  View details for PubMedCentralID PMC3470612

• Toward MR-guided high intensity focused ultrasound for presurgical localization: Focused ultrasound lesions in cadaveric breast tissue JOURNAL OF MAGNETIC RESONANCE IMAGING Bitton, R. R., Kaye, E., Dirbas, F. M., Daniel, B. L., Pauly, K. B. 2012; 35 (5): 1089-1097

  Abstract

  To investigate magnetic resonance image-guided high intensity focused ultrasound (MR-HIFU) as a surgical guide for nonpalpable breast tumors by assessing the palpability of MR-HIFU-created lesions in ex vivo cadaveric breast tissue.MR-HIFU ablations spaced 5 mm apart were made in 18 locations using the ExAblate2000 system. Ablations formed a square perimeter in mixed adipose and fibroglandular tissue. Ablation was monitored using T1-weighted fast spin echo images. MR-acoustic radiation force impulse (MR-ARFI) was used to remotely palpate each ablation location, measuring tissue displacement before and after thermal sonications. Displacement profiles centered at each ablation spot were plotted for comparison. The cadaveric breast was manually palpated to assess stiffness of ablated lesions and dissected for gross examination. This study was repeated on three cadaveric breasts.MR-ARFI showed a collective postablation reduction in peak displacement of 54.8% ([4.41 ± 1.48] μm pre, [1.99 ± 0.82] μm post), and shear wave velocity increase of 65.5% ([10.69 ± 1.60] mm pre, [16.33 ± 3.10] mm post), suggesting tissue became stiffer after the ablation. Manual palpation and dissection of the breast showed increased palpability, a darkening of ablation perimeter, and individual ablations were visible in mixed adipose/fibroglandular tissue.The results of this preliminary study show MR-HIFU has the ability to create palpable lesions in ex vivo cadaveric breast tissue, and may potentially be used to preoperatively localize nonpalpable breast tumors.

  View details for DOI 10.1002/jmri.23529

  View details for PubMedID 22170814

• Transcranial Phase Aberration Correction Using Beam Simulations and MR-ARFI 12th International Symposium on Therapeutic Ultrasound Vyas, U., Kaye, E., Pauly, K. B. AMER INST PHYSICS. 2012: 185–190

  View details for DOI 10.1063/1.4769941

  View details for Web of Science ID 000312416000035

• Ultrashort TE Imaging of Cryotherapy EMAGRES Lu, A., Daniel, B. L., Pauly, K. 2012; 1 (3): 539–50

  View details for DOI 10.1002/9780470034590.emrstm1279

  View details for Web of Science ID 000218751100008

• Rapid HIFU autofocusing using the entire MR-ARFI image 12th International Symposium on Therapeutic Ultrasound Grissom, W. A., Kaye, E., Pauly, K. B., Zur, Y., Yeo, D., Medan, Y., Davis, C. AMER INST PHYSICS. 2012: 162–167

  View details for DOI 10.1063/1.4769936

  View details for Web of Science ID 000312416000030

• MRI of Frozen Tissue Demonstrates a Phase Shift MAGNETIC RESONANCE IN MEDICINE Lu, A., Daniel, B. L., Kaye, E., Pauly, K. B. 2011; 66 (6): 1582-1589

  Abstract

  While temperature mapping is desired during cryosurgery for prostate cancer treatment, an effective approach for this purpose is still needed. We have demonstrated a phase shift with temperature in our in vivo canine experiments and ex vivo tissue sample experiments within the frozen tissue. The phase shift is much larger (~0.7 °/°C with an echo time of 0.1 ms at 0.5 T) in magnitude than that predicted by conventional proton resonant frequency shift (0.008 °/°C). It shows little dependence on the echo times used and thus is not due to a frequency change, although frequency-dependent phase shift has been observed near the frozen tissue. This phase shift varies monotonically with temperature within the frozen tissue and therefore may be potentially used as a novel temperature mapping approach in cryoablation applications.

  View details for DOI 10.1002/mrm.22953

  View details for Web of Science ID 000297285000012

  View details for PubMedID 21630347

  View details for PubMedCentralID PMC3166360

• MR Imaging-guided Cryoablation for the Treatment of Benign Prostatic Hyperplasia JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY Ghanouni, P., Gill, H., Kaye, E., Pauly, K. B., Daniel, B. 2011; 22 (10): 1427-1430

  Abstract

  A patient with benign prostatic hyperplasia presented with chronic lower urinary tract symptoms despite prior surgery and continued medical therapy. Using a magnetic resonance imaging-guided transperineal approach, two cryoprobes were placed into the transition zone of the prostate gland, and two cryoablation freeze-thaw cycles were performed. At 10 weeks after treatment, the frequency of nocturia had decreased from once every 1.5 hours to once per night, urinary peak flow rates had increased from 5.1 mL/s to 10.3 mL/s, and postvoid residual urinary bladder volume had decreased from 187 mL to 58 mL. Improved flow rates and symptoms remained stable 16 weeks after treatment.

  View details for DOI 10.1016/j.jvir.2011.08.010

  View details for PubMedID 21961982

• Metal-Induced Artifacts in MRI AMERICAN JOURNAL OF ROENTGENOLOGY Hargreaves, B. A., Worters, P. W., Pauly, K. B., Pauly, J. M., Koch, K. M., Gold, G. E. 2011; 197 (3): 547-555

  Abstract

  The purpose of this article is to review some of the basic principles of imaging and how metal-induced susceptibility artifacts originate in MR images. We will describe common ways to reduce or modify artifacts using readily available imaging techniques, and we will discuss some advanced methods to correct readout-direction and slice-direction artifacts.The presence of metallic implants in MRI can cause substantial image artifacts, including signal loss, failure of fat suppression, geometric distortion, and bright pile-up artifacts. These cause large resonant frequency changes and failure of many MRI mechanisms. Careful parameter and pulse sequence selections can avoid or reduce artifacts, although more advanced imaging methods offer further imaging improvements.

  View details for DOI 10.2214/AJR.11.7364

  View details for Web of Science ID 000294165600037

  View details for PubMedID 21862795

• In vivo MR acoustic radiation force imaging in the porcine liver MEDICAL PHYSICS Holbrook, A. B., Ghanouni, P., Santos, J. M., Medan, Y., Pauly, K. B. 2011; 38 (9): 5081-5089

  Abstract

  High intensity focused ultrasound (HIFU) in the abdomen can be sensitive to acoustic aberrations that can exist in the beam path of a single sonication. Having an accurate method to quickly visualize the transducer focus without damaging tissue could assist with executing the treatment plan accurately and predicting these changes and obstacles. By identifying these obstacles, MR acoustic radiation force imaging (MR-ARFI) provides a reliable method for visualizing the transducer focus quickly without damaging tissue and allows accurate execution of the treatment plan.MR-ARFI was used to view the HIFU focus, using a gated spin echo flyback readout-segmented echo-planar imaging sequence. HIFU spots in a phantom and in the livers of five live pigs under general anesthesia were created with a 550 kHz extracorporeal phased array transducer initially localized with a phase-dithered MR-tracking sequence to locate microcoils embedded in the transducer. MR-ARFI spots were visualized, observing the change of focal displacement and ease of steering. Finally, MR-ARFI was implemented as the principle liver HIFU calibration system, and MR-ARFI measurements of the focal location relative to the thermal ablation location in breath-hold and breathing experiments were performed.Measuring focal displacement with MR-ARFI was achieved in the phantom and in vivo liver. In one in vivo experiment, where MR-ARFI images were acquired repeatedly at the same location with different powers, the displacement had a linear relationship with power [y = 0.04x + 0.83 μm (R(2) = 0.96)]. In another experiment, the displacement images depicted the electronic steering of the focus inside the liver. With the new calibration system, the target focal location before thermal ablation was successfully verified. The entire calibration protocol delivered 20.2 J of energy to the animal (compared to greater than 800 J for a test thermal ablation). ARFI displacement maps were compared with thermal ablations during seven breath-hold ablations. The error was 0.83 ± 0.38 mm in the S/I direction and 0.99 ± 0.45 mm in the L/R direction. For six spots in breathing ablations, the mean error in the nonrespiration direction was 1.02 ± 0.89 mm.MR-ARFI has the potential to improve free-breathing plan execution accuracy compared to current calibration and acoustic beam adjustment practices. Gating the acquisition allows for visualization of the focal spot over the course of respiratory motion, while also being insensitive to motion effects that can complicate a thermal test spot. That MR-ARFI measures a mechanical property at the focus also makes it insensitive to high perfusion, of particular importance to highly perfused organs such as the liver.

  View details for DOI 10.1118/1.3622610

  View details for Web of Science ID 000294482900019

  View details for PubMedID 21978053

  View details for PubMedCentralID PMC3170397

• Magnetic resonance guided high-intensity focused ultrasound ablation of musculoskeletal tumors. Current orthopaedic practice Avedian, R. S., Gold, G., Ghanouni, P., Pauly, K. B. 2011; 22 (4): 303-308

  Abstract

  This article reviews the fundamental principles and clinical experimental uses of magnetic resonance guided high-intensity focused ultrasound (MRgHIFU) ablation of musculoskeletal tumors. MRgHIFU is a noninvasive treatment modality that takes advantage of the ability of magnetic resonance to measure tissue temperature and uses this technology to guide high-intensity focused ultrasound waves to a specific focus within the human body that results in heat generation and complete thermal necrosis of the targeted tissue. Adjacent normal tissues are spared because of the accurate delivery of thermal energy, as well as, local blood perfusion that provides a cooling effect. MRgHIFU is approved by the Food and Drug Administration for the treatment of uterine fibroids and is used on an experimental basis to treat breast, prostate, liver, bone, and brain tumors.

  View details for PubMedID 26120376

• Magnetic resonance guided high-intensity focused ultrasound ablation of musculoskeletal tumors CURRENT ORTHOPAEDIC PRACTICE Avedian, R. S., Gold, G., Ghanouni, P., Pauly, K. 2011; 22 (4): 303–8

  View details for DOI 10.1097/BCO.0b013e318220dad5

  View details for Web of Science ID 000217802900004

• Slice Encoding for Metal Artifact Correction With Noise Reduction MAGNETIC RESONANCE IN MEDICINE Lu, W., Pauly, K. B., Gold, G. E., Pauly, J. M., Hargreaves, B. A. 2011; 65 (5): 1352-1357

  Abstract

  Magnetic resonance imaging (MRI) near metallic implants is often hampered by severe metal artifacts. To obtain distortion-free MR images near metallic implants, SEMAC (Slice Encoding for Metal Artifact Correction) corrects metal artifacts via robust encoding of excited slices against metal-induced field inhomogeneities, followed by combining the data resolved from multiple SEMAC-encoded slices. However, as many of the resolved data elements only contain noise, SEMAC-corrected images can suffer from relatively low signal-to-noise ratio. Improving the signal-to-noise ratio of SEMAC-corrected images is essential to enable SEMAC in routine clinical studies. In this work, a new reconstruction procedure is proposed to reduce noise in SEMAC-corrected images. A singular value decomposition denoising step is first applied to suppress quadrature noise in multi-coil SEMAC-encoded slices. Subsequently, the singular value decomposition-denoised data are selectively included in the correction of through-plane distortions. The experimental results demonstrate that the proposed reconstruction procedure significantly improves the SNR without compromising the correction of metal artifacts.

  View details for DOI 10.1002/mrm.22796

  View details for Web of Science ID 000289760800018

  View details for PubMedID 21287596

  View details for PubMedCentralID PMC3079010

• Rapid MR-ARFI Method for Focal Spot Localization During Focused Ultrasound Therapy MAGNETIC RESONANCE IN MEDICINE Kaye, E. A., Chen, J., Pauly, K. B. 2011; 65 (3): 738-743

  Abstract

  MR-guided focused ultrasound (FUS) is a noninvasive therapy for treating various pathologies. MR-based acoustic radiation force imaging (MR-ARFI) measures tissue displacement in the focal spot due to acoustic radiation force. MR-ARFI also provides feedback for adaptive focusing algorithms that could correct for phase aberrations caused by the skull during brain treatments. This work developed a single-shot echo-planar imaging-based MR-ARFI method that reduces scan time and ultrasound energy deposition. The new method was implemented and tested in a phantom and ex vivo brain tissue. The effect of the phase aberrations on the ultrasound focusing was studied using displacement maps obtained with echo-planar imaging and two-dimensional spin-warp MR-ARFI. The results show that displacement in the focal spot can be rapidly imaged using echo-planar imaging-based MR-ARFI with high signal-to-noise ratio efficiency and without any measurable tissue heating. Echo-planar imaging-based displacement images also demonstrate sufficient sensitivity to phase aberrations and can serve as rapid feedback for adaptive focusing in brain treatments and other applications.

  View details for DOI 10.1002/mrm.22662

  View details for Web of Science ID 000287929800016

  View details for PubMedID 21337406

• MR-Guided Unfocused Ultrasound Disruption of the Rat Blood-Brain Barrier 10th International Symposium on Therapeutic Ultrasound Townsend, K. A., King, R. L., Zaharchuk, G., Pauly, K. B. AMER INST PHYSICS. 2011: 356–360

  View details for DOI 10.1063/1.3607933

  View details for Web of Science ID 000295944900059

• Fabrication of CMUT Cells with Gold Center Mass for Higher Output Pressure 10th International Symposium on Therapeutic Ultrasound Yoon, H., Ho, M., Apte, N., Cristman, P., Vaithilingam, S., Kupnik, M., Butts-Pauly, K., Khuri-Yakub, B. T. AMER INST PHYSICS. 2011: 183–188

  View details for DOI 10.1063/1.3607902

  View details for Web of Science ID 000295944900028

• Reweighted l(1) Referenceless PRF Shift Thermometry MAGNETIC RESONANCE IN MEDICINE Grissom, W. A., Lustig, M., Holbrook, A. B., Rieke, V., Pauly, J. M., Butts-Pauly, K. 2010; 64 (4): 1068-1077

  Abstract

  Temperature estimation in proton resonance frequency (PRF) shift MR thermometry requires a reference, or pretreatment, phase image that is subtracted from image phase during thermal treatment to yield a phase difference image proportional to temperature change. Referenceless thermometry methods derive a reference phase image from the treatment image itself by assuming that in the absence of a hot spot, the image phase can be accurately represented in a smooth (usually low order polynomial) basis. By masking the hot spot out of a least squares (ℓ(2)) regression, the reference phase image's coefficients on the polynomial basis are estimated and a reference image is derived by evaluating the polynomial inside the hot spot area. Referenceless methods are therefore insensitive to motion and bulk main field shifts, however, currently these methods require user interaction or sophisticated tracking to ensure that the hot spot is masked out of the polynomial regression. This article introduces an approach to reference PRF shift thermometry that uses reweighted ℓ(1) regression, a form of robust regression, to obtain background phase coefficients without hot spot tracking and masking. The method is compared to conventional referenceless thermometry, and demonstrated experimentally in monitoring HIFU heating in a phantom and canine prostate, as well as in a healthy human liver.

  View details for DOI 10.1002/mrm.22502

  View details for Web of Science ID 000282477100015

  View details for PubMedID 20564600

  View details for PubMedCentralID PMC3155729

• Magnetic Resonance Imaging Near Metal Implants JOURNAL OF MAGNETIC RESONANCE IMAGING Koch, K. M., Hargreaves, B. A., Pauly, K. B., Chen, W., Gold, G. E., King, K. F. 2010; 32 (4): 773-787

  Abstract

  The desire to apply magnetic resonance imaging (MRI) techniques in the vicinity of embedded metallic hardware is increasing. The soft-tissue contrast available with MR techniques is advantageous in diagnosing complications near an increasing variety of MR-safe metallic hardware. Near such hardware, the spatial encoding mechanisms utilized in conventional MRI methods are often severely compromised. Mitigating these encoding difficulties has been the focus of numerous research investigations over the past two decades. Such approaches include view-angle tilting, short echo-time projection reconstruction acquisitions, single-point imaging, prepolarized MRI, and postprocessing image correction. Various technical advances have also enabled the recent development of two alternative approaches that have shown promising clinical potential. Here, the physical principals and proposed solutions to the problem of MRI near embedded metal are discussed.

  View details for DOI 10.1002/jmri.22313

  View details for Web of Science ID 000282764800002

  View details for PubMedID 20882607

• Hybrid referenceless and multibaseline subtraction MR thermometry for monitoring thermal therapies in moving organs MEDICAL PHYSICS Grissom, W. A., Rieke, V., Holbrook, A. B., Medan, Y., Lustig, M., Santos, J., McConnell, M. V., Pauly, K. B. 2010; 37 (9): 5014-5026

  Abstract

  Magnetic resonance thermometry using the proton resonance frequency (PRF) shift is a promising technique for guiding thermal ablation. For temperature monitoring in moving organs, such as the liver and the heart, problems with motion must be addressed. Multi-baseline subtraction techniques have been proposed, which use a library of baseline images covering the respiratory and cardiac cycle. However, main field shifts due to lung and diaphragm motion can cause large inaccuracies in multi-baseline subtraction. Referenceless thermometry methods based on polynomial phase regression are immune to motion and susceptibility shifts. While referenceless methods can accurately estimate temperature within the organ, in general, the background phase at organ/tissue interfaces requires large polynomial orders to fit, leading to increased danger that the heated region itself will be fitted by the polynomial and thermal dose will be underestimated. In this paper, a hybrid method for PRF thermometry in moving organs is presented that combines the strengths of referenceless and multi-baseline thermometry.The hybrid image model assumes that three sources contribute to image phase during thermal treatment: Background anatomical phase, spatially smooth phase deviations, and focal, heat-induced phase shifts. The new model and temperature estimation algorithm were tested in the heart and liver of normal volunteers, in a moving phantom HIFU heating experiment, and in numerical simulations of thermal ablation. The results were compared to multi-baseline and referenceless methods alone.The hybrid method allows for in vivo temperature estimation in the liver and the heart with lower temperature uncertainty compared to multi-baseline and referenceless methods. The moving phantom HIFU experiment showed that the method accurately estimates temperature during motion in the presence of smooth main field shifts. Numerical simulations illustrated the method's sensitivity to algorithm parameters and hot spot features.This new hybrid method for MR thermometry in moving organs combines the strengths of both multi-baseline subtraction and referenceless thermometry and overcomes their fundamental weaknesses.

  View details for DOI 10.1118/1.3475943

  View details for PubMedID 20964221

• T-2 relaxation times of C-13 metabolites in a rat hepatocellular carcinoma model measured in vivo using C-13-MRS of hyperpolarized [1-C-13]pyruvate NMR IN BIOMEDICINE Yen, Y., Le Roux, P., Mayer, D., King, R., Spielman, D., Tropp, J., Pauly, K. B., Pfefferbaum, A., Vasanawala, S., Hurd, R. 2010; 23 (4): 414-423

  Abstract

  A single-voxel Carr-Purcell-Meibloom-Gill sequence was developed to measure localized T(2) relaxation times of (13)C-labeled metabolites in vivo for the first time. Following hyperpolarized [1-(13)C]pyruvate injections, pyruvate and its metabolic products, alanine and lactate, were observed in the liver of five rats with hepatocellular carcinoma and five healthy control rats. The T(2) relaxation times of alanine and lactate were both significantly longer in HCC tumors than in normal livers (p < 0.002). The HCC tumors also showed significantly higher alanine signal relative to the total (13)C signal than normal livers (p < 0.006). The intra- and inter-subject variations of the alanine T(2) relaxation time were 11% and 13%, respectively. The intra- and inter-subject variations of the lactate T(2) relaxation time were 6% and 7%, respectively. The intra-subject variability of alanine to total carbon ratio was 16% and the inter-subject variability 28%. The intra-subject variability of lactate to total carbon ratio was 14% and the inter-subject variability 20%. The study results show that the signal level and relaxivity of [1-(13)C]alanine may be promising biomarkers for HCC tumors. Its diagnostic values in HCC staging and treatment monitoring are yet to be explored.

  View details for DOI 10.1002/nbm.1481

  View details for Web of Science ID 000277525800011

  View details for PubMedID 20175135

  View details for PubMedCentralID PMC2891253

• Optimization of Encoding Gradients for MR-ARFI MAGNETIC RESONANCE IN MEDICINE Chen, J., Watkins, R., Pauly, K. B. 2010; 63 (4): 1050-1058

  Abstract

  MR acoustic radiation force imaging provides a promising method to monitor therapeutic ultrasound treatments. By measuring the displacement induced by the acoustic radiation force, MR acoustic radiation force imaging can locate the focal spot, without a significant temperature rise. In this work, the encoding gradient for MR acoustic radiation force imaging is optimized to achieve an enhanced accuracy and precision of the displacement measurement. By analyzing the sources of artifacts, bulk motion and eddy currents are shown to introduce errors to the measurement, and heavy diffusion-weighting is shown to result in noisy displacement maps. To eliminate these problems, a new encoding scheme is proposed, which utilizes a pair of bipolar gradients. Improved precision is achieved with robustness against bulk motion and background phase distortion, and improved accuracy is achieved with reduced diffusion-weighting and optimized encoding pulse width. The experiment result shows that the signal-to-noise ratio can be enhanced by more than 2-fold. These significant improvements are obtained at no cost of scan time or encoding sensitivity, enabling the detection of a displacement less than 0.l microm in a gel phantom with MR acoustic radiation force imaging.

  View details for DOI 10.1002/mrm.22299

  View details for Web of Science ID 000276064300023

  View details for PubMedID 20373406

  View details for PubMedCentralID PMC2852270

• Accelerated Slice Encoding for Metal Artifact Correction JOURNAL OF MAGNETIC RESONANCE IMAGING Hargreaves, B. A., Chen, W., Lu, W., Alley, M. T., Gold, G. E., Brau, A. C., Pauly, J. M., Pauly, K. B. 2010; 31 (4): 987-996

  Abstract

  To demonstrate accelerated imaging with both artifact reduction and different contrast mechanisms near metallic implants.Slice-encoding for metal artifact correction (SEMAC) is a modified spin echo sequence that uses view-angle tilting and slice-direction phase encoding to correct both in-plane and through-plane artifacts. Standard spin echo trains and short-TI inversion recovery (STIR) allow efficient PD-weighted imaging with optional fat suppression. A completely linear reconstruction allows incorporation of parallel imaging and partial Fourier imaging. The signal-to-noise ratio (SNR) effects of all reconstructions were quantified in one subject. Ten subjects with different metallic implants were scanned using SEMAC protocols, all with scan times below 11 minutes, as well as with standard spin echo methods.The SNR using standard acceleration techniques is unaffected by the linear SEMAC reconstruction. In all cases with implants, accelerated SEMAC significantly reduced artifacts compared with standard imaging techniques, with no additional artifacts from acceleration techniques. The use of different contrast mechanisms allowed differentiation of fluid from other structures in several subjects.SEMAC imaging can be combined with standard echo-train imaging, parallel imaging, partial-Fourier imaging, and inversion recovery techniques to offer flexible image contrast with a dramatic reduction of metal-induced artifacts in scan times under 11 minutes.

  View details for DOI 10.1002/jmri.22112

  View details for Web of Science ID 000276328200026

  View details for PubMedID 20373445

  View details for PubMedCentralID PMC2894155

• Consistency of Signal Intensity and T2*in Frozen Ex Vivo Heart Muscle, Kidney, and Liver Tissue JOURNAL OF MAGNETIC RESONANCE IMAGING Kaye, E. A., Josan, S., Lu, A., Rosenberg, J., Daniel, B. L., Pauly, K. B. 2010; 31 (3): 719-724

  Abstract

  To investigate tissue dependence of the MRI-based thermometry in frozen tissue by quantification and comparison of signal intensity and T2* of ex vivo frozen tissue of three different types: heart muscle, kidney, and liver.Tissue samples were frozen and imaged on a 0.5 Tesla MRI scanner with ultrashort echo time (UTE) sequence. Signal intensity and T2* were determined as the temperature of the tissue samples was decreased from room temperature to approximately -40 degrees C. Statistical analysis was performed for (-20 degrees C, -5 degrees C) temperature interval.The findings of this study demonstrate that signal intensity and T2* are consistent across three types of tissue for (-20 degrees C, -5 degrees C) temperature interval.Both parameters can be used to calculate a single temperature calibration curve for all three types of tissue and potentially in the future serve as a foundation for tissue-independent MRI-based thermometry.

  View details for DOI 10.1002/jmri.22029

  View details for PubMedID 20187218

• Real-Time MR Thermometry for Monitoring HIFU Ablations of the Liver MAGNETIC RESONANCE IN MEDICINE Holbrook, A. B., Santos, J. M., Kaye, E., Rieke, V., Pauly, K. B. 2010; 63 (2): 365-373

  Abstract

  A high-resolution and high-speed pulse sequence is presented for monitoring high-intensity focused ultrasound ablations in the liver in the presence of motion. The sequence utilizes polynomial-order phase saturation bands to perform outer volume suppression, followed by spatial-spectral excitation and three readout segmented echo-planar imaging interleaves. Images are processed with referenceless thermometry to create temperature-rise images every frame. The sequence and reconstruction were implemented in RTHawk and used to image stationary and moving sonications in a polyacrylamide gel phantom (62.4 acoustic W, 50 sec, 550 kHz). Temperature-rise images were compared between moving and stationary experiments. Heating spots and corresponding temperature-rise plots matched very well. The stationary sonication had a temperature standard deviation of 0.15 degrees C compared to values of 0.28 degrees C and 0.43 degrees C measured for two manually moved sonications at different velocities. Moving the phantom (while not heating) with respect to the transducer did not cause false temperature rises, despite susceptibility changes. The system was tested on nonheated livers of five normal volunteers. The mean temperature rise was -0.05 degrees C, with a standard deviation of 1.48 degrees C. This standard deviation is acceptable for monitoring high-intensity focused ultrasound ablations, suggesting real-time imaging of moving high-intensity focused ultrasound sonications can be clinically possible.

  View details for DOI 10.1002/mrm.22206

  View details for Web of Science ID 000273995200013

  View details for PubMedID 19950255

  View details for PubMedCentralID PMC3212435

• Clinical feasibility of a magnetic resonance tracking system to guide the position of the scan plane during physiologic joint motion RADIOLOGIA MEDICA Vandevenne, J., Pearle, A., Lang, P., Pauly, K. B., Bergman, G. 2010; 115 (1): 133-140

  Abstract

  Unrestricted physiologic joint motion results in multidirectional displacement of the anatomic structures. When performing real-time magnetic resonance (MR) imaging of such a joint motion, continuous adjustment of the scan plane position may be required. The purpose of this study was to evaluate the clinical feasibility of a method to guide the scan plane position during dynamic-motion MR imaging of freely moving joints.The location of a small tracker device (dedicated hardware) placed on the patient's skin overlying a joint was determined by an ultrashort MR sequence and used to automatically adjust the scan plane position prior to each dynamic-motion MR image. Using a vertically open MR unit, this MR tracking system was applied in ten dynamic-motion MR examinations to evaluate flexion/extension manoeuvres in the weight-bearing knee joint, and in ten dynamic-motion MR examinations of the shoulder joint to evaluate manoeuvres such as internal/external rotation of the humerus, stress testing of the glenohumeral joint and abduction/adduction manoeuvres. Average number of manoeuvre repetitions, total number of images and percentage of useful images per manoeuvre were calculated. Imaging time per scan plane for each manoeuvre was recorded.Average repetition of manoeuvres varied between 1.6 and 5.8, with an average number of 7 to 18 images per manoeuvre. Average percentage of useful images varied between 61% and 89%. Total imaging time per scan plane ranged between 1 min 10 s and 4 min 51 s.The MR tracking system to guide the slice position for each consecutive dynamic-motion MR image of the freely but slowly moving shoulder or knee joint was feasible for clinical use, providing a high percentage of useful images for each manoeuvre within a clinically acceptable time frame.

  View details for DOI 10.1007/s11547-009-0485-4

  View details for Web of Science ID 000274915400011

  View details for PubMedID 20041313

• Capacitive Micromachined Ultrasonic Transducers for Therapeutic Ultrasound Applications IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING Wong, S. H., Kupnik, M., Watkins, R. D., Butts-Pauly, K., Khuri-Yakub, B. T. 2010; 57 (1): 114-123

  Abstract

  Therapeutic ultrasound guided by MRI is a noninvasive treatment that potentially reduces mortality, lowers medical costs, and widens accessibility of treatments for patients. Recent developments in the design and fabrication of capacitive micromachined ultrasonic transducers (CMUTs) have made them competitive with piezoelectric transducers for use in therapeutic ultrasound applications. In this paper, we present the first designs and prototypes of an eight-element, concentric-ring, CMUT array to treat upper abdominal cancers. This array was simulated and designed to focus 30-50 mm into tissue, and ablate a 2- to 3-cm-diameter tumor within 1 h. Assuming a surface acoustic output pressure of 1 MPa peak-to-peak (8.5 W/cm (2)) at 2.5 MHz, we simulated an array that produced a focal intensity of 680 W/cm (2) when focusing to 35 mm. CMUT cells were then designed to meet these frequency and surface acoustic intensity specifications. These cell designs were fabricated as 2.5 mm x 2.5 mm test transducers and used to verify our models. The test transducers were shown to operate at 2.5 MHz with an output pressure of 1.4 MPa peak-to-peak (16.3 W/cm (2)). With this CMUT cell design, we fabricated a full eight-element array. Due to yield issues, we only developed electronics to focus the four center elements of the array. The beam profile of the measured array deviated from the simulated one because of the crosstalk effects; the beamwidth matched within 10% and sidelobes increased by two times, which caused the measured gain to be 16.6 compared to 27.4.

  View details for DOI 10.1109/TBME.2009.2026909

  View details for Web of Science ID 000273565600018

  View details for PubMedID 19628448

• Rapid MR-ARFI method for focal spot localization during focused ultrasound treatments 9th International Symposium on Therapeutic Ultrasound Kaye, E., Chen, J., Pauly, K. B. AMER INST PHYSICS. 2010: 247–250

  View details for Web of Science ID 000280794100056

• Alternative Focal Spot Geometry for More Efficient HIFU Treatment Assessment 9th International Symposium on Therapeutic Ultrasound Kaye, E., Chen, J., Medan, Y., Pauly, K. B. AMER INST PHYSICS. 2010: 256–259

  View details for Web of Science ID 000280794100058

• Effect of the Rat Skull On Focused US, as Measured by MR Thermometry 9th International Symposium on Therapeutic Ultrasound King, R., Rieke, V., Pauly, K. B. AMER INST PHYSICS. 2010: 387–390

  View details for Web of Science ID 000280794100088

• Maximum Linear-Phase Spectral-Spatial Radiofrequency Pulses for Fat-Suppressed Proton Resonance Frequency-Shift MR Thermometry MAGNETIC RESONANCE IN MEDICINE Grissom, W. A., Kerr, A. B., Holbrook, A. B., Pauly, J. M., Butts-Pauly, K. 2009; 62 (5): 1242-1250

  Abstract

  Conventional spectral-spatial pulses used for water-selective excitation in proton resonance frequency-shift MR thermometry require increased sequence length compared to shorter wideband pulses. This is because spectral-spatial pulses are longer than wideband pulses, and the echo time period starts midway through them. Therefore, for a fixed echo time, one must increase sequence length to accommodate conventional spectral-spatial pulses in proton resonance frequency-shift thermometry. We introduce improved water-selective spectral-spatial pulses for which the echo time period starts near the beginning of excitation. Instead of requiring increased sequence length, these pulses extend into the long echo time periods common to PRF sequences. The new pulses therefore alleviate the traditional tradeoff between sequence length and fat suppression. We experimentally demonstrate an 11% improvement in frame rate in a proton resonance frequency imaging sequence compared to conventional spectral-spatial excitation. We also introduce a novel spectral-spatial pulse design technique that is a hybrid of previous model- and filter-based techniques and that inherits advantages from both. We experimentally validate the pulses' performance in suppressing lipid signal and in reducing sequence length compared to conventional spectral-spatial pulses.

  View details for DOI 10.1002/mrm.22118

  View details for Web of Science ID 000271431200018

  View details for PubMedID 19780177

  View details for PubMedCentralID PMC2795148

• A strategy for blood biomarker amplification and localization using ultrasound PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA D'Souza, A. L., Tseng, J. R., Pauly, K. B., Guccione, S., Rosenberg, J., Gambhir, S. S., Glazer, G. M. 2009; 106 (40): 17152-17157

  Abstract

  Blood biomarkers have significant potential applications in early detection and management of various diseases, including cancer. Most biomarkers are present in low concentrations in blood and are difficult to discriminate from noise. Furthermore, blood measurements of a biomarker do not provide information about the location(s) where it is produced. We hypothesize a previously undescribed strategy to increase the concentration of biomarkers in blood as well as localize the source of biomarker signal using ultrasound energy directly applied to tumor cells. We test and validate our hypothesis in cell culture experiments and mouse tumor xenograft models using the human colon cancer cell line LS174T, while measuring the biomarker carcinoembryonic antigen (CEA) before and after the use of ultrasound to liberate the biomarker from the tumor cells. The results demonstrate that the application of low-frequency ultrasound to tumor cells causes a significant release of tumor biomarker, which can be measured in the blood. Furthermore, we establish that this release is specific to the direct application of the ultrasound to the tumor, enabling a method for localization of biomarker production. This work shows that it is possible to use ultrasound to amplify and localize the source of CEA levels in blood of tumor-bearing mice and will allow for a previously undescribed way to determine the presence and localization of disease more accurately using a relatively simple and noninvasive strategy.

  View details for DOI 10.1073/pnas.0903437106

  View details for Web of Science ID 000270537500053

  View details for PubMedID 19805109

  View details for PubMedCentralID PMC2749842

• 3.0-T MR-Guided Focused Ultrasound for Preoperative Localization of Nonpalpable Breast Lesions: An Initial Experimental Ex Vivo Study JOURNAL OF MAGNETIC RESONANCE IMAGING Schmitz, A. C., Van den Bosch, M. A., Rieke, V., Dirbas, F. M., Pauly, K. B., Mali, W. P., Daniel, B. L. 2009; 30 (4): 884-889

  Abstract

  To compare the accuracy of magnetic resonance-guided focused ultrasound (MRgFUS) with MR-guided needle-wire placement (MRgNW) for the preoperative localization of nonpalpable breast lesions.In this experimental ex vivo study, 15 turkey breasts were used. In each breast phantom an artificial nonpalpable "tumor" was created by injecting an aqueous gel containing gadolinium. MRgFUS (n = 7) was performed with the ExAblate 2000 system (InSightec). With MRgFUS the ablated tissue changes in color and increases in stiffness. A rim of palpable and visible ablations was created around the tumor to localize the tumor and facilitate excision. MRgNW (n = 8) was performed by MR-guided placement of an MR-compatible needle-wire centrally in the tumor. After surgical excision of the tumor, MR images were used to evaluate tumor-free margins (negative/positive), minimum tumor-free margin (mm), and excised tissue volume (cm(3)).With MRgFUS localization no positive margins were found after excision (0%). With MRgNW two excision specimens (25%) had positive margins (P = 0.48). Mean minimum tumor-free margin (+/-SD) with MRgFUS was significantly larger (5.5 +/- 2.4 mm) than with MRgNW (0.9 +/- 1.4 mm) (P < 0.001). Mean volume +/- SD of excised tissue did not differ between MRgFUS and MRgNW localization, ie, 44.0 +/- 9.4 cm(3) and 39.5 +/- 10.7 cm(3) (P = 0.3).The results of this experimental ex vivo study indicate that MRgFUS can potentially be used to localize nonpalpable breast lesions in vivo.

  View details for DOI 10.1002/jmri.21896

  View details for PubMedID 19787736

• SEMAC: Slice Encoding for Metal Artifact Correction in MRI 16th Annual Meeting of the International-Society-of-Magnetic-Resonance-in-Medicine Lu, W., Pauly, K. B., Gold, G. E., Pauly, J. M., Hargreaves, B. A. WILEY-BLACKWELL. 2009: 66–76

  Abstract

  Magnetic resonance imaging (MRI) near metallic implants remains an unmet need because of severe artifacts, which mainly stem from large metal-induced field inhomogeneities. This work addresses MRI near metallic implants with an innovative imaging technique called "Slice Encoding for Metal Artifact Correction" (SEMAC). The SEMAC technique corrects metal artifacts via robust encoding of each excited slice against metal-induced field inhomogeneities. The robust slice encoding is achieved by extending a view-angle-tilting (VAT) spin-echo sequence with additional z-phase encoding. Although the VAT compensation gradient suppresses most in-plane distortions, the z-phase encoding fully resolves distorted excitation profiles that cause through-plane distortions. By positioning all spins in a region-of-interest to their actual spatial locations, the through-plane distortions can be corrected by summing up the resolved spins in each voxel. The SEMAC technique does not require additional hardware and can be deployed to the large installed base of whole-body MRI systems. The efficacy of the SEMAC technique in eliminating metal-induced distortions with feasible scan times is validated in phantom and in vivo spine and knee studies.

  View details for DOI 10.1002/mrm.21967

  View details for Web of Science ID 000267404300008

  View details for PubMedID 19267347

  View details for PubMedCentralID PMC2837371

• MRI-Guided Cryoablation: In Vivo Assessment of Focal Canine Prostate Cryolesions JOURNAL OF MAGNETIC RESONANCE IMAGING Josan, S., Bouley, D. M., van den Bosch, M., Daniel, B. L., Pauly, K. B. 2009; 30 (1): 169-176

  Abstract

  To analyze the appearance of acute and chronic canine prostate cryolesions on T1-weighted (T1w) and T2-weighted (T2w) magnetic resonance imaging (MRI) and compare them with contrast-enhanced (CE) MRI and histology for a variety of freezing protocols.Three different freezing protocols were used in canine prostate cryoablation experiments. Six acute and seven chronic (survival times ranging between 4-53 days) experiments were performed. The change in T2w signal intensity was correlated with freezing protocol parameters. The lesion area on T2w MRI was compared to CE-MRI. Histopathologic evaluation of the cryolesions was performed and visually compared to the appearance on MRI.The T2w signal increased from pre- to postfreeze at the site of the cryolesion, and the enhancement was higher for smaller freeze area and duration. The T2w lesion area was between the CE nonperfused area and the hyperenhancing CE rim. The appearance of the lesion on T1w and T2w imaging over time correlated with outcome on pathology.T1w and T2w MRI can potentially be used to assess cryolesions and to monitor tissue response over time following cryoablation.

  View details for DOI 10.1002/jmri.21827

  View details for PubMedID 19557805

• Changes in posterior lumbar disk contour abnormality with flexion-extension movement in subjects with low back pain and degenerative disk disease. PM & R : the journal of injury, function, and rehabilitation Lee, S., Lee, J., Butts, K., Carragee, E., Fredericson, M. 2009; 1 (6): 541-546

  Abstract

  To determine whether posterior lumbar disk contour dimensions differ in the flexed seated, upright seated, and extended seated positions.Two subgroups of subjects with degenerative disk disease were compared: those with central posterior disk bulge (at L4-5 or L5-S1 levels) and those with a dark nucleus pulposus without posterior disk bulge (L3-4, L4-5, and/or L5-S1 levels).Academic medical center.Eight subjects with a central disk bulge and 9 subjects with a dark nucleus pulposus on magnetic resonance imaging.Not applicable.Quantitative comparisons of posterior disk contour between neutral, flexed, and extended sitting positions.Of 8 subjects with central disk bulge, spinal flexion (from the neutral position) produced a decreased disk contour in all subjects, whereas spinal extension (from the neutral position) produced an increased disk contour in 6 subjects, a decreased disk contour in 1 subject, and no measurable change in 1 subject. Changes in posterior disk contour in subjects with a dark nucleus pulposus were variable. Approximately half increased and half decreased, but no relation to position was determined.The results of this pilot study suggest a consistent pattern of decreased posterior disk contour with spinal flexion and increased posterior disk contour with spinal extension in subjects with central disk bulge, but not in those with a dark nucleus pulposus.

  View details for DOI 10.1016/j.pmrj.2009.03.014

  View details for PubMedID 19627944

• Changes in Posterior Lumbar Disk Contour Abnormality with Flexion-Extension Movement in Subjects with Low Back Pain and Degenerative Disk Disease PM&R Lee, S., Lee, J., Butts, K., Carragee, E., Fredericson, M. 2009; 1 (6): 541-546

  Abstract

  To determine whether posterior lumbar disk contour dimensions differ in the flexed seated, upright seated, and extended seated positions.Two subgroups of subjects with degenerative disk disease were compared: those with central posterior disk bulge (at L4-5 or L5-S1 levels) and those with a dark nucleus pulposus without posterior disk bulge (L3-4, L4-5, and/or L5-S1 levels).Academic medical center.Eight subjects with a central disk bulge and 9 subjects with a dark nucleus pulposus on magnetic resonance imaging.Not applicable.Quantitative comparisons of posterior disk contour between neutral, flexed, and extended sitting positions.Of 8 subjects with central disk bulge, spinal flexion (from the neutral position) produced a decreased disk contour in all subjects, whereas spinal extension (from the neutral position) produced an increased disk contour in 6 subjects, a decreased disk contour in 1 subject, and no measurable change in 1 subject. Changes in posterior disk contour in subjects with a dark nucleus pulposus were variable. Approximately half increased and half decreased, but no relation to position was determined.The results of this pilot study suggest a consistent pattern of decreased posterior disk contour with spinal flexion and increased posterior disk contour with spinal extension in subjects with central disk bulge, but not in those with a dark nucleus pulposus.

  View details for DOI 10.1016/j.pmrj.2009.03.014

  View details for Web of Science ID 000208411600006

• Double Half RF Pulses for Reduced Sensitivity to Eddy Currents in UTE Imaging MAGNETIC RESONANCE IN MEDICINE Josan, S., Pauly, J. M., Daniel, B. L., Pauly, K. B. 2009; 61 (5): 1083-1089

  Abstract

  Ultrashort echo time imaging with half RF pulse excitation is challenging as eddy currents induced by the slice-select gradient distort the half pulse slice profile. This work presents two pulses with T(2)-dependent slice profiles that are less sensitive to eddy currents. The double half pulse improves the slice selectivity for long T(2) components, while the inverted double half pulse suppresses the unwanted long T(2) signal. Thus, both approaches prevent imperfect cancellation of out-of-slice signal from contaminating the desired slice. Experimental results demonstrate substantially improved slice selectivity and R(2)* quantitation accuracy with these pulses. These pulses are effective in making short T(2) imaging and quantitation less sensitive to eddy currents and provide an alternative to time-consuming gradient characterization.

  View details for DOI 10.1002/mrm.21879

  View details for PubMedID 19235919

• Improved Half RF Slice Selectivity in the Presence of Eddy Currents with Out-of-Slice Saturation MAGNETIC RESONANCE IN MEDICINE Josan, S., Kaye, E., Pauly, J. M., Daniel, B. L., Pauly, K. B. 2009; 61 (5): 1090-1095

  Abstract

  Ultrashort echo time imaging with half RF pulse excitation is sensitive to eddy currents induced by the slice-select gradient that distorts the half pulse slice profile. This work demonstrates improvements in the half pulse profile by using spatial saturation on both sides of the imaged slice to suppress the out-of-slice magnetization. This effectively improves the selectivity of the half pulse excitation profile. A quadratic phase RF pulse with high bandwidth and selectivity was used to achieve a wide saturation band with sharp edges. Experimental results demonstrate substantially improved slice selectivity and R(2)* quantitation accuracy obtained with the out-of-slice saturation. This approach is effective in making short T(2) imaging and quantitation with half pulses less sensitive to eddy currents.

  View details for DOI 10.1002/mrm.21914

  View details for PubMedID 19319972

• MR Imaging-guided Percutaneous Cryoablation of the Prostate in an Animal Model: In Vivo Imaging of Cryoablation-induced Tissue Necrosis with Immediate Histopathologic Correlation 32nd Annual Meeting of the Society-of-Interventional-Radiology (SIR) van den Bosch, M. A., Josan, S., Bouley, D. M., Chen, J., Gill, H., Rieke, V., Butts-Pauly, K., Daniel, B. L. ELSEVIER SCIENCE INC. 2009: 252–58

  Abstract

  To evaluate the feasibility of magnetic resonance (MR) imaging-guided percutaneous cryoablation of normal canine prostates and to identify MR imaging features that accurately predict the area of tissue damage at a microscopic level.Six adult male mixed-breed dogs were anesthetized, intubated, and placed in a 0.5-T open MR imaging system. A receive-only endorectal coil was placed, and prostate location and depth were determined on T1-weighted fast spin-echo (FSE) MR imaging. After placement of cryoprobes and temperature sensors, three freezing protocols were used to ablate prostate tissue. Ice ball formation was monitored with T1-weighted FSE imaging. Tissue necrosis area was assessed with contrast-enhanced weighted MR imaging and compared with histopathologic findings.A total of 12 cryolesions (mean size, 1.2 cm) were bilaterally created in six prostates. Ice ball formation was oval and signal-free on T1-weighted FSE sequences in all cases. Postprocedural contrast-enhanced MR imaging typically showed a nonenhancing area of low signal intensity centrally located within the frozen area, surrounded by a bright enhancing rim in all cases. On histopathologic examination, two distinct zones were identified within cryolesions. Centrally, a necrotic zone with complete cellular destruction and hemorrhage was found. Between this necrotic zone and normal glandular tissue, a zone of fragmented and intact glands, interstitial edema, and rare acute inflammatory cells was seen. Correlation between nonenhancement on contrast-enhanced weighted MR images and tissue necrosis on pathologic examination was consistent within all six dogs.MR imaging-guided cryoablation of the prostate is technically feasible. The nonenhancing area on postablation contrast-enhanced weighted MR imaging accurately predicts the area of cryoablation-induced tissue necrosis on pathologic analysis.

  View details for DOI 10.1016/j.jvir.2008.10.030

  View details for PubMedID 19091600

• MR-guidance of HIFU Therapy Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society Pauly, K. B., Rieke, V., Holbrook, A. B., Grissom, W., Chen, J., Kaye, E. IEEE. 2009: 141–144

  Abstract

  MR guidance of high intensity focused ultrasound is evolving with each new application. In this paper we describe ongoing research in the MR-guidance aspect of MR-guided focused ultrasound. The structure is divided into the pretreatment/setup phase of the procedure, MR thermometry for monitoring the actual treatment, and methods for assessment and follow-up.

  View details for Web of Science ID 000280543600037

  View details for PubMedID 19964927

• Optimization of Encoding Gradients for Magnetic Resonance Acoustic Radiation Force Imaging 8th International Symposium on Therapeutic Ultras Chen, J., Watkins, R., Pauly, K. B. AMER INST PHYSICS. 2009: 275–278

  View details for Web of Science ID 000266425300053

• Progress in Development of HIFU CMUTs for use under MR-guidance 8th International Symposium on Therapeutic Ultras Wong, S. H., Watkins, R. D., Kupnik, M., Pauly, K. B., Khuri-Yakub, B. T. AMER INST PHYSICS. 2009: 327–331

  View details for Web of Science ID 000266425300063

• Catheter-Based Ultrasound for 3D Control of Thermal Therapy 8th International Symposium on Therapeutic Ultras Diederich, C., Chen, X., Wootton, J., Juang, T., Nau, W. H., Kinsey, A., Hsu, I., Rieke, V., Pauly, K. B., Sommer, G., Bouley, D. AMER INST PHYSICS. 2009: 318–322

  View details for Web of Science ID 000266425300061

• Fast Referenceless PRF Thermometry Using Spatially Saturated, Spatial-spectrally Excited Flyback EPI. 8th International Symposium on Therapeutic Ultras Holbrook, A. B., Kaye, E., Santos, J. M., Rieke, V., Pauly, K. B. AMER INST PHYSICS. 2009: 223–227

  View details for Web of Science ID 000266425300042

• REGULARIZED REFERENCELESS TEMPERATURE ESTIMATION IN PRF-SHIFT MR THERMOMETRY IEEE International Symposium on Biomedical Imaging - From Nano to Macro Grissom, W., Pauly, K. B., Lustig, M., Rieke, V., Pauly, J., McDannold, N. IEEE. 2009: 1235–1238

  View details for Web of Science ID 000270678400316

• The Feasibility of HIFU Liver Ablation Through the Ribcage and Cartilage in a Rodent Model 8th International Symposium on Therapeutic Ultras King, R., Rieke, V., Pauly, K. B. AMER INST PHYSICS. 2009: 149–153

  View details for Web of Science ID 000266425300028

• All-in-one magnetic resonance arthrography of the shoulder in a vertically open magnetic resonance unit ACTA RADIOLOGICA Vandevenne, J. E., Vanhoenacker, F., Beaulieu, C. F., Bergman, A. G., Pauly, K. B., Dillingham, M. F., Lang, P. K. 2008; 49 (8): 918-927

  Abstract

  Magnetic resonance (MR) arthrography frequently involves joint injection under imaging guidance followed by MR imaging in static positions.To evaluate if MR arthrography of the shoulder joint can be performed in a comprehensive fashion combining the MR-guided injection procedure, static MR imaging, and dynamic motion MR imaging in a single test.Twenty-three shoulder joints were injected with Gd-DTPA2- under MR guidance. Static MR imaging was performed and included a three-point Dixon method to achieve water-selective images. Dynamic motion MR imaging with and without applying pressure to the upper arm was used to evaluate glenohumeral joint instability. In 10 cases, surgical correlation was available.The all-in-one MR arthrography technique was successful in all patients, and took an average time of 65 min. All but one glenohumeral injection procedure were performed with a single needle pass, and no complications were observed. Out of eight labrum tears seen with static MR imaging, seven were confirmed at surgery. In 10 cases, dynamic motion MR imaging correlated well with the surgeon's intraoperative evaluation for presence and direction of instability.MR arthrography of the shoulder joint using a vertically open magnet can be performed as a single comprehensive test, including the injection and the static and dynamic motion MR imaging. Good diagnostic accuracy for intraarticular lesions and glenohumeral instability was found in a small sample.

  View details for DOI 10.1080/02841850802291242

  View details for Web of Science ID 000260046200011

  View details for PubMedID 18651257

• Evaluation of wafer bonded CMUTs with rectangular membranes featuring high fill factor IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Wong, S. H., Kupnik, M., Zhuang, X., Lin, D., Butts-Pauly, K., Khuri-Yakub, B. T. 2008; 55 (9): 2053-2065

  Abstract

  Increasing fill factor is one design approach used to increase average output displacement, output pressure, and sensitivity of capacitive micromachined ultrasonic transducers (CMUTs). For rectangular cells, the cell-to-cell spacing and the aspect ratio determine the fill factor. In this paper, we explore the effects of these parameters on performance, in particular the nonuniformity of collapse voltage between neighboring cells and presence of higher order modes in air or immersed operation. We used a white light interferometer to measure nonuniformity in deflection between neighboring cells. We found that reducing the cell-to-cell spacing could cause bending of the center support post, which amplifies nonuniformities in collapse voltage to 18.4% between neighboring cells. Using a 2-D finite element model (FEM), we found that for our designs, increasing the support post width to 1.67 times the membrane thickness alleviated the post bending problem. Using impedance and interferometer measurements to observe the effects of aspect ratio on higher order modes, we found that the (1,3) modal frequency approached the (1,1) modal frequency as the aspect ratio of the rectangles increased. In air operation, under continuous wave (CW) excitation at the center frequency, the rectangular cells behaved in the (1,1) mode. In immersion, because of dispersive guided modes, these cells operated in a higher order mode when excited with a CW signal at the center frequency. This contributed to a loss of output pressure; for this reason our rectangular design was unsuitable for CW operation in immersion.

  View details for DOI 10.1109/TUFFC.897

  View details for Web of Science ID 000258912800020

  View details for PubMedID 18986902

  View details for PubMedCentralID PMC2766518

• Improved slice selection for R2*mapping during cryoablation with eddy current compensation JOURNAL OF MAGNETIC RESONANCE IMAGING Lu, A., Daniel, B. L., Pauly, J. M., Pauly, K. B. 2008; 28 (1): 190-198

  Abstract

  To improve the slice profile and image quality of R2* mapping in the iceball during cryoablation with ultrashort echo time (UTE) imaging by compensating for eddy currents induced by the selective gradient when half-pulse radiofrequency (RF) excitation is employed to achieve UTEs.A method to measure both B0 and linear eddy currents simultaneously is first presented. This is done with a least-square fitting process on calibration data collected on a phantom. Eddy currents during excitation are compensated by redesigning the RF pulse and the selective gradient accordingly, while that resultant from the readout gradient are compensated for during image reconstruction. In vivo data were obtained continuously during the cryoablation experiments to calculate the R2* values in the iceball and to correlate them with the freezing process.Image quality degradation due to eddy currents is significantly reduced with the proposed approaches. R2* maps of iceball throughout the cryoablation experiments were achieved with improved quality.The proposed approaches are effective for compensating eddy currents during half-pulse RF excitation as well as readout. TEs as short as 100 microsec were obtained, allowing R2* maps to be obtained from frozen tissues with improved quality.

  View details for DOI 10.1002/jmri.21396

  View details for PubMedID 18581340

• Monitoring prostate thermal therapy with diffusion-weighted MRI MAGNETIC RESONANCE IN MEDICINE Chen, J., Daniel, B. L., Diederich, C. J., Bouley, D. M., Van den Bosch, M. A., Kinsey, A. M., Sommer, G., Pauly, K. B. 2008; 59 (6): 1365-1372

  Abstract

  For MR-guided minimally invasive therapies, it is important to have a repeatable and reliable tissue viability evaluation method. The use of diffusion-weighted MRI (DWI) to evaluate tissue damage was assessed in 19 canine prostates with cryoablation or high-intensity ultrasound (HIU) ablation. The apparent diffusion coefficient (ADC) trace value was measured in the treated tissue immediately upon the procedure and on the posttreatment follow-up. For the acute lesions, the ADC value decreased to (1.05+/-0.25)x10(-3) mm2/s, as compared to (1.64+/-0.24)x10(-3) mm2/s before the treatment. There was no statistical difference between previously frozen or previously ultrasound-heated lesions in terms of the 36% ADC reduction (P=0.66). The ADC decrease occurred early during the course of the treatment, which appears to complicate DWI-based thermometry. Over time, the ADC value increased as the tissue recovered and regenerated. This study shows that DWI could be a promising method to monitor prostate thermal therapies and to provide insight on tissue damage and tissue remodeling after injury.

  View details for DOI 10.1002/mrm.21589

  View details for PubMedID 18506801

• Transurethral ultrasound applicators with dynamic multi-sector control for prostate thermal therapy: In vivo evaluation under MR guidance MEDICAL PHYSICS Kinsey, A. M., Diederich, C. J., Rieke, V., Nau, W. H., Pauly, K. B., Bouley, D., Sommer, G. 2008; 35 (5): 2081-2093

  Abstract

  The purpose of this study was to explore the feasibility and performance of a multi-sectored tubular array transurethral ultrasound applicator for prostate thermal therapy, with potential to provide dynamic angular and length control of heating under MR guidance without mechanical movement of the applicator. Test configurations were fabricated, incorporating a linear array of two multi-sectored tubular transducers (7.8-8.4 MHz, 3 mm OD, 6 mm length), with three 120 degrees independent active sectors per tube. A flexible delivery catheter facilitated water cooling (100 ml min(-1)) within an expandable urethral balloon (35 mm long x 10 mm diameter). An integrated positioning hub allows for rotating and translating the transducer assembly within the urethral balloon for final targeting prior to therapy delivery. Rotational beam plots indicate approximately 90 degrees-100 degrees acoustic output patterns from each 120 degrees transducer sector, negligible coupling between sectors, and acoustic efficiencies between 41% and 53%. Experiments were performed within in vivo canine prostate (n = 3), with real-time MR temperature monitoring in either the axial or coronal planes to facilitate control of the heating profiles and provide thermal dosimetry for performance assessment. Gross inspection of serial sections of treated prostate, exposed to TTC (triphenyl tetrazolium chloride) tissue viability stain, allowed for direct assessment of the extent of thermal coagulation. These devices created large contiguous thermal lesions (defined by 52 degrees C maximum temperature, t43 = 240 min thermal dose contours, and TTC tissue sections) that extended radially from the applicator toward the border of the prostate (approximately15 mm) during a short power application (approximately 8-16 W per active sector, 8-15 min), with approximately 200 degrees or 360 degrees sector coagulation demonstrated depending upon the activation scheme. Analysis of transient temperature profiles indicated progression of lethal temperature and thermal dose contours initially centered on each sector that coalesced within approximately 5 min to produce uniform and contiguous zones of thermal destruction between sectors, with smooth outer boundaries and continued radial propagation in time. The dimension of the coagulation zone along the applicator was well-defined by positioning and active array length. Although not as precise as rotating planar and curvilinear devices currently under development for MR-guided procedures, advantages of these multi-sectored transurethral applicators include a flexible delivery catheter and that mechanical manipulation of the device using rotational motors is not required during therapy. This multi-sectored tubular array transurethral ultrasound technology has demonstrated potential for relatively fast and reasonably conformal targeting of prostate volumes suitable for the minimally invasive treatment of BPH and cancer under MR guidance, with further development warranted.

  View details for DOI 10.1118/1.2900131

  View details for Web of Science ID 000255456500049

  View details for PubMedID 18561684

  View details for PubMedCentralID PMC2673638

• Feasibility of MR-temperature mapping of ultrasonic heating from a CMUT IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL Wong, S. H., Watkins, R. D., Kupnik, M., Pauly, K. B., Khuri-Yakub, B. T. 2008; 55 (4): 811-818

  Abstract

  In the last decade, high intensity focused ultrasound (HIFU) has gained popularity as a minimally invasive and noninvasive therapeutic tool for treatment of cancers, arrhythmias, and other medical conditions. HIFU therapy is often guided by magnetic resonance imaging (MRI), which provides anatomical images for therapeutic device placement, temperature maps for treatment guidance, and postoperative evaluation of the region of interest. While piezoelectric transducers are dominantly used for MR-guided HIFU, capacitive micromachined ultrasonic transducers (CMUTs) show competitive advantages, such as ease of fabrication, integration with electronics, improved efficiency, and reduction of self-heating. In this paper, we will show our first results of an unfocused CMUT transducer monitored by MR-temperature maps. This 2.51 mm by 2.32 mm, unfocused CMUT heated a HIFU phantom by 14 degrees C in 2.5 min. This temperature rise was successfully monitored by MR thermometry in a 3.0 T General Electric scanner.

  View details for DOI 10.1109/TUFFC.2008.71.5

  View details for Web of Science ID 000254783100007

  View details for PubMedID 18467225

• Echo combination to reduce proton resonance frequency (PRF) thermometry errors from fat JOURNAL OF MAGNETIC RESONANCE IMAGING Rieke, V., Pauly, K. B. 2008; 27 (3): 673-677

  Abstract

  To validate echo combination as a means to reduce errors caused by fat in temperature measurements with the proton resonance frequency (PRF) shift method.Computer simulations were performed to study the behavior of temperature measurement errors introduced by fat as a function of echo time. Error reduction by combining temperature images acquired at different echo times was investigated. For experimental verification, three echoes were acquired in a refocused gradient echo acquisition. Temperature images were reconstructed with the PRF shift method for the three echoes and then combined in a weighted average. Temperature measurement errors in the combined image and the individual echoes were compared for pure water and different fractions of fat in a computer simulation and for a phantom containing a homogenous mixture with 20% fat in an MR experiment.In both simulation and MR measurement, the presence of fat caused severe temperature underestimation or overestimation in the individual echoes. The errors were substantially reduced after echo combination. Residual errors were about 0.3 degrees C for 10% fat and 1 degrees C for 20% fat.Echo combination substantially reduces temperature measurement errors caused by small fractions of fat. This technique then eliminates the need for fat suppression in tissues such as the liver.

  View details for DOI 10.1002/jmri.21238

  View details for Web of Science ID 000253949300035

  View details for PubMedID 18064715

  View details for PubMedCentralID PMC2780361

• Design, performance, and applications of a hybrid X-Ray/MR system for interventional guidance PROCEEDINGS OF THE IEEE Fahrig, R., Ganguly, A., Lillaney, P., Bracken, J., Rowlands, J. A., Wen, Z., Yu, H., Rieke, V., Santos, J. M., Pauly, K. B., Sze, D. Y., Frisoli, J. K., Daniel, B. L., Pelc, N. J. 2008; 96 (3): 468-480

  View details for DOI 10.1109/JPROC.2007.913506

  View details for Web of Science ID 000253299600007

• MR thermometry JOURNAL OF MAGNETIC RESONANCE IMAGING Rieke, V., Pauly, K. B. 2008; 27 (2): 376-390

  Abstract

  Minimally invasive thermal therapy as local treatment of benign and malignant diseases has received increasing interest in recent years. Safety and efficacy of the treatment require accurate temperature measurement throughout the thermal procedure. Noninvasive temperature monitoring is feasible with magnetic resonance (MR) imaging based on temperature-sensitive MR parameters such as the proton resonance frequency (PRF), the diffusion coefficient (D), T1 and T2 relaxation times, magnetization transfer, the proton density, as well as temperature-sensitive contrast agents. In this article the principles of temperature measurements with these methods are reviewed and their usefulness for monitoring in vivo procedures is discussed. Whereas most measurements give a temperature change relative to a baseline condition, temperature-sensitive contrast agents and spectroscopic imaging can provide absolute temperature measurements. The excellent linearity and temperature dependence of the PRF and its near independence of tissue type have made PRF-based phase mapping methods the preferred choice for many in vivo applications. Accelerated MRI imaging techniques for real-time monitoring with the PRF method are discussed. Special attention is paid to acquisition and reconstruction methods for reducing temperature measurement artifacts introduced by tissue motion, which is often unavoidable during in vivo applications.

  View details for DOI 10.1002/jmri.21265

  View details for Web of Science ID 000252909100014

  View details for PubMedID 18219673

  View details for PubMedCentralID PMC2780364

• MRI-guided radiofrequency ablation of breast cancer: Preliminary clinical experience JOURNAL OF MAGNETIC RESONANCE IMAGING van den Bosch, M., Daniel, B., Rieke, V., Butts-Pauly, K., Kermit, E., Jeffrey, S. 2008; 27 (1): 204-208

  Abstract

  This study was designed to demonstrate the feasibility of MRI-guided radiofrequency ablation (RFA) of breast cancer. A total of three women diagnosed with invasive ductal breast cancer were treated with percutaneous MRI-guided RFA, according to a treat and resect protocol, in our hospital. RFA procedures were performed in an open 0.5T Signa-SP imager allowing direct patient access and real-time monitoring of the procedure. In all patients ablation was performed with a 15-gauge insulated MRI-compatible multiple needle probe. MRI thermometry and contrast-enhanced postablation MRI were used to evaluate the ablation process. Patients underwent lumpectomy within a week of the RFA procedure. Histopathology confirmed successful (100%) tumor ablation in one patient, and partial tumor destruction (33% and 50%, respectively) in two patients. Challenges of MRI-guided breast RFA that need to be solved to facilitate progress of the technique toward clinical practice are discussed.

  View details for DOI 10.1002/jmri.21190

  View details for PubMedID 18050333

• Progress in CMUTs for HIFU ablation of upper abdominal cancer IEEE Ultrasonics Symposium Wong, S. H., Kupnik, M., Khuri-Yakub, B. T., Watkins, R. D., Pauly, K. B. IEEE. 2008: 2068–2071

  View details for Web of Science ID 000268845801102

• Catheter-Based Ultrasound Devices and MR Thermal Monitoring for Conformal Prostate Thermal Therapy 30th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society Diederich, C. J., Nau, W. H., Kinsey, A., Ross, T., Wootton, J., Juang, T., Butts-Pauly, K., Rieke, V., Chen, J., Bouley, D. M., Sommer, G. IEEE. 2008: 3664–3668

  Abstract

  Catheter-based ultrasound applicators have been developed for delivering hyperthermia or high-temperature thermal ablation of cancer and benign disease of the prostate. These devices allow for control of heating along the length and angular expanse during therapy delivery. Four types of transurethral applicators were devised for thermal treatment of prostate combined with MR thermal monitoring: sectored tubular transducer devices with directional heating patterns and rotation; planar and curvilinear devices with narrow heating patterns and rotation; and multi-sectored tubular devices capable of dynamic angular control without applicator movement. Interstitial devices (2.4 mm OD) have been developed for percutaneous implantation with directional or dynamic angular control. In vivo experiments in canine prostate under MR temperature imaging were used to evaluate these devices and develop treatment delivery strategies. MR thermal imaging was used to monitor temperature and thermal dose in multiple slices through the target volume. Multi-sectored transurethral applicators can dynamically control the angular heating profile and target large regions of the gland in short treatment times without applicator manipulation. The sectored tubular, planar, and curvilinear transurethral devices produce directional coagulation zones, extending 15-20 mm radial distance to the outer prostate capsule. Sequential rotation under motor control and modulated dwell time can be used to tightly conform thermal ablation to selected regions. Interstitial implants with directional devices can be used to effectively ablate targeted regions of the gland while protecting the rectum. The MR derived 52 degrees C and lethal thermal dose contours (t43=240 min) effectively defined the extent of thermal damage and provided a means for real-time control of the applicators. Catheter-based ultrasound devices, combined with MR thermal monitoring, can produce relatively fast (5-40 min) and precise thermal ablation of prostate.

  View details for Web of Science ID 000262404502111

  View details for PubMedID 19163505

• REDUCTION OF METAL ARTEFACTS IN MUSCULOSKELETAL MR IMAGING JBR-BTR Vandevenne, J. E., Vanhoenacker, F. M., Parizel, R. M., Pauly, K. B., Lang, P. K. 2007; 90 (5): 345-349

  Abstract

  The purpose of this article is to present a educational overview of practical tips to deal with metal artefacts in clinical musculoskeletal MRI. A brief theoretical explanation to understand the cause of metal artefacts is provided followed by a discussion on parameters to reduce these metal artefacts. Effects of adjustable parameters are demonstrated both in a volunteer with a titanium screw and a saline bag attached to the shoulder and in a in vitro experiment. These parameters include positioning of the patient with the long axis of metallic hardware parallel to B0, use of fast spin echo sequences, use of inversion recovery fat suppression, swapping phase and frequency encoding direction, use of view angle tilting, increasing the read-out bandwidth, and decreasing voxel size.

  View details for Web of Science ID 000260089300008

  View details for PubMedID 18085188

• MRI-guided thermal ablation therapy: Model and parameter estimates to predict cell death from MR thermometry images ANNALS OF BIOMEDICAL ENGINEERING Breen, M. S., Breen, M., Butts, K., Chen, L., Saidel, G. M., Wilson, D. L. 2007; 35 (8): 1391-1403

  Abstract

  Solid tumors and other pathologies can be treated using laser thermal ablation under interventional magnetic resonance imaging (iMRI) guidance. A model was developed to predict cell death from magnetic resonance (MR) thermometry measurements based on the temperature-time history, and validated using in vivo rabbit brain data. To align post-ablation T2-weighted spin-echo MR lesion images to gradient-echo MR images, from which temperature is derived, a registration method was used that aligned fiducials placed near the thermal lesion. The outer boundary of the hyperintense rim in the post-ablation MR lesion image was used as the boundary for cell death, as verified from histology. Model parameters were simultaneously estimated using an iterative optimization algorithm applied to every interesting voxel in 328 images from multiple experiments having various temperature histories. For a necrotic region of 766 voxels across all lesions, the model provided a voxel specificity and sensitivity of 98.1 and 78.5%, respectively. Mislabeled voxels were typically within one voxel from the segmented necrotic boundary with median distances of 0.77 and 0.22 mm for false positives (FP) and false negatives (FN), respectively. As compared to the critical temperature cell death model and the generalized Arrhenius model, our model typically predicted fewer FP and FN. This is good evidence that iMRI temperature maps can be used with our model to predict therapeutic regions in real-time during treatment.

  View details for DOI 10.1007/s10439-007-9300-3

  View details for Web of Science ID 000248054500009

  View details for PubMedID 17436111

• Quantitative evaluation of the relaxivity effects of iodine on Gd-DTPA enhanced MR arthrography JOURNAL OF MAGNETIC RESONANCE IMAGING Ganguly, A., Gold, G. E., Pauly, K. B., Mayer, D., Moseley, M. M., Pelc, N. J., Fahrig, R. 2007; 25 (6): 1219-1225

  Abstract

  To quantify the effect of iodine on the gadolinium (Gd) contrast-enhanced signal in MR arthrography.Saline solutions of Gd contrast agent (0-1 mmol/liter) were mixed with iodinated contrast agent (0-185 mmol/liter). The T1 and T2 relaxation constants of these solutions were measured at 1.5T. Different types of commonly used iodinated contrast agents as well as sodium iodide (NaI) solutions were also analyzed.Iodine caused significant T2 shortening and some T1 shortening in Gd contrast solutions. Both contrast agents independently obeyed the standard relaxation relation, and their mixture obeyed a modified version of this relation. The side chains in various iodine molecules and their viscosities affected the relaxation properties differently. For various spin-echo (SE) sequences, the signal from synovial fluid containing different concentrations of the two contrast agents was calculated. The T2-weighted signal appeared to be most affected by the increase in iodine concentrations. In the absence of Gd contrast, all SE sequences showed an initial increase in signal from iodine contrast.A generalized relation for the relaxivities of Gd contrast in the presence of iodine was established. The side chains of iodine contrast were found to alter the relaxivities of Gd contrast. Imaging with proton density (PD)-weighted SE with only iodine contrast agent was found to be feasible.

  View details for DOI 10.1002/jmri.20934

  View details for Web of Science ID 000246824100017

  View details for PubMedID 17520728

• Referenceless MR thermometry for monitoring thermal ablation in the prostate IEEE TRANSACTIONS ON MEDICAL IMAGING Rieke, V., Kinsey, A. M., Ross, A. B., Nau, W. H., Diederich, C. J., Sommer, G., Pauly, K. B. 2007; 26 (6): 813-821

  Abstract

  Referenceless proton resonance frequency (PRF) shift thermometry provides a means to measure temperature changes during minimally invasive thermotherapy that is inherently robust to motion and tissue displacement. However, if the referenceless method is used to determine temperature changes during prostate ablation, phase gaps between water and fat in image regions used to determine the background phase can confound the phase estimation. We demonstrate an extension to referenceless thermometry which eliminates this problem by allowing background phase estimation in the presence of phase discontinuities between aqueous and fatty tissue. In this method, images are acquired with a multiecho sequence and binary water and fat maps are generated from a Dixon reconstruction. For the background phase estimation, water and fat regions are treated separately and the phase offset between the two tissue types is determined. The method is demonstrated feasibile in phantoms and during in vivo thermal ablation of canine prostate.

  View details for DOI 10.1109/TMI.2007.892647

  View details for PubMedID 17679332

• Correlation of contrast-enhanced MR images with the histopathology of minimally invasive thermal and cryoablation cancer treatments in normal dog prostates. Proceedings of SPIE--the International Society for Optical Engineering Bouley, D. M., Daniel, B., Pauly, K. B., Liu, E., Kinsey, A., NAU, W., Diederich, C. J., Sommer, G. 2007; 6440: 644006-?

  Abstract

  Magnetic Resonance Imaging (MRI) is a promising tool for visualizing the delivery of minimally invasive cancer treatments such as high intensity ultrasound (HUS) and cryoablation. We use an acute dog prostate model to correlate lesion histopathology with contrast-enhanced (CE) T1 weighted MR images, to aid the radiologists in real time interpretation of in vivo lesion boundaries and pre-existing lesions. Following thermal or cryo treatments, prostate glands are removed, sliced, stained with the vital dye triphenyl tetrazolium chloride, photographed, fixed and processed in oversized blocks for routine microscopy. Slides are scanned by Trestle Corporation at .32 microns/pixel resolution, the various lesions traced using annotation software, and digital images compared to CE MR images. Histologically, HUS results in discrete lesions characterized by a "heat-fixed" zone, in which glands subjected to the highest temperatures are minimally altered, surrounded by a rim or "transition zone" composed of severely fragmented, necrotic glands, interstitial edema and vascular congestion. The "heat-fixed" zone is non-enhancing on CE MRI while the "transition zone" appears as a bright, enhancing rim. Likewise, the CE MR images for cryo lesions appear similar to thermally induced lesions, yet the histopathology is significantly different. Glands subjected to prolonged freezing appear totally disrupted, coagulated and hemorrhagic, while less intensely frozen glands along the lesion edge are partially fragmented and contain apoptotic cells. In conclusion, thermal and cryo-induced lesions, as well as certain pre-existing lesions (cystic hyperplasia - non-enhancing, chronic prostatitis - enhancing) have particular MRI profiles, useful for treatment and diagnostic purposes.

  View details for PubMedID 25076818

• Segmental lumbar mobility in individuals with low back pain: in vivo assessment during manual and self-imposed motion using dynamic MRI BMC MUSCULOSKELETAL DISORDERS Kulig, K., Powers, C. M., Landel, R. F., Chen, H., Fredericson, M., Guillet, M., Butts, K. 2007; 8

  Abstract

  Altered spinal mobility is thought to be related to current or past episodes of low back pain; however evidence of that relationship in younger subjects has not been established. The purpose of this study was to compare lumbar segmental mobility in asymptomatic and symptomatic subjects during posterior to anterior (PA) manual spinal mobilization and a self-initiated prone press-up (PU) maneuver. We hypothesized that persons with central low back pain would have an altered lumbar segmental mobility pattern compared to those without pain.Forty-five individuals (age 32.1 +/- 8.5) with non-specific low back pain and 20 persons (age 31.1 +/- 7.0) without low back pain participated. Each subject underwent dynamic imaging of the lumbar spine during a PA mobilization procedure and while performing a PU. Segmental motion was quantified as the change in the intervertebral angle between the resting and end-range vertebral positions.The symptomatic group had a larger percentage of subjects with evidence of single level segmental hypermobility than the asymptomatic group during the PA (40.0% vs. 5%) and PU (26.7% vs. 15%) procedures. Single lumbar motion-segment analysis revealed hyper-mobility in symptomatic subjects at L5 - S1 (Chi-square = 10.0, p < or = 0.01) and L4 - L5 (Chi-square = 4.18, p < or = 0.05) during the PA test.Persons with non-specific low back pain have a tendency to demonstrate single level lumbar segmental hypermobility when compared to age specific asymptomatic subjects.

  View details for DOI 10.1186/1471-2474-8-8

  View details for Web of Science ID 000244076100001

  View details for PubMedID 17261197

  View details for PubMedCentralID PMC1794409

• Advantages of capacitive micromachined ultrasonics transducers (CMUTs) for high intensity focused ultrasound (HIFU) IEEE Ultrasonics Symposium Wong, S. H., Kupnik, M., Butts-Pauly, K., Khuri-Yakub, B. T. IEEE. 2007: 1313–1316

  View details for Web of Science ID 000254281801078

• Prostate thermal therapy with catheter-based ultrasound devices and MR thermal monitoring Conference on Thermal Treatment of Tissue - Energy Delivery and Assessment IV Diederich, C. J., Nau, W. H., Kinsey, A., Ross, T., Wootton, J., Juang, T., Butts-Pauly, K., Ricke, V., Liu, E. H., Chen, J., Bouley, D. M., van den Bosch, M., Sommer, G. SPIE-INT SOC OPTICAL ENGINEERING. 2007

  View details for DOI 10.1117/12.703184

  View details for Web of Science ID 000246494100009

• Design of HIFUCMUT arrays for treatment of liver and renal cancer 6th International Symposium on Therapeutic Ultrasound Wong, S. H., Ergun, A. S., Yaralioglu, G. G., Oralkan, O., Kupnik, M., Pauly, K. B., Khuri-Yakub, B. T. AMER INST PHYSICS. 2007: 54–60

  View details for Web of Science ID 000247342200009

• Fast conformal thermal ablation in the prostate with transurethral multi-sectored ultrasound devices and MR guidance 6th International Symposium on Therapeutic Ultrasound Kinsey, A. M., Diederich, C. J., Nau, W. H., Ross, A. B., Pauly, K. B., Rieke, V., Sommer, G. AMER INST PHYSICS. 2007: 400–404

  View details for Web of Science ID 000247342200062

• Segmentation of costal cartilage in abdominal CT data using watershed markers 6th International Symposium on Therapeutic Ultrasound Holbrook, A. B., Pauly, K. B. AMER INST PHYSICS. 2007: 226–231

  View details for Web of Science ID 000247342200035

• Referenceless PRF thermometry with multi-echo processing to monitor prostate ablation 6th International Symposium on Therapeutic Ultrasound Rieke, V., Kinsey, A. M., Nau, W. H., Diederich, C. J., Sommer, G., Pauly, K. B. AMER INST PHYSICS. 2007: 272–277

  View details for Web of Science ID 000247342200042

• Correlation of contrast-enhanced NM images with the histopathology of minimally invasive thermal and cryoablation cancer treatments in normal dog prostates Conference on Thermal Treatment of Tissue - Energy Delivery and Assessment IV Bouley, D. M., Daniel, B., Butts Pauly, K., Liu, E., Kinse, A., NAU, W., Diederich, C. J., Sommer, G. SPIE-INT SOC OPTICAL ENGINEERING. 2007

  Abstract

  Magnetic Resonance Imaging (MRI) is a promising tool for visualizing the delivery of minimally invasive cancer treatments such as high intensity ultrasound (HUS) and cryoablation. We use an acute dog prostate model to correlate lesion histopathology with contrast-enhanced (CE) T1 weighted MR images, to aid the radiologists in real time interpretation of in vivo lesion boundaries and pre-existing lesions. Following thermal or cryo treatments, prostate glands are removed, sliced, stained with the vital dye triphenyl tetrazolium chloride, photographed, fixed and processed in oversized blocks for routine microscopy. Slides are scanned by Trestle Corporation at .32 microns/pixel resolution, the various lesions traced using annotation software, and digital images compared to CE MR images. Histologically, HUS results in discrete lesions characterized by a "heat-fixed" zone, in which glands subjected to the highest temperatures are minimally altered, surrounded by a rim or "transition zone" composed of severely fragmented, necrotic glands, interstitial edema and vascular congestion. The "heat-fixed" zone is non-enhancing on CE MRI while the "transition zone" appears as a bright, enhancing rim. Likewise, the CE MR images for cryo lesions appear similar to thermally induced lesions, yet the histopathology is significantly different. Glands subjected to prolonged freezing appear totally disrupted, coagulated and hemorrhagic, while less intensely frozen glands along the lesion edge are partially fragmented and contain apoptotic cells. In conclusion, thermal and cryo-induced lesions, as well as certain pre-existing lesions (cystic hyperplasia - non-enhancing, chronic prostatitis - enhancing) have particular MRI profiles, useful for treatment and diagnostic purposes.

  View details for DOI 10.1117/12.701049

  View details for Web of Science ID 000246494100005

  View details for PubMedCentralID PMC4112763

• Evaluation of thermal and cryo lesions by diffusion-weighted MRI Conference on Thermal Treatment of Tissue - Energy Delivery and Assessment IV Chen, J., Daniel, B., Bouley, D., Sommer, G., Butts Pauly, K. SPIE-INT SOC OPTICAL ENGINEERING. 2007

  View details for DOI 10.1117/12.703255

  View details for Web of Science ID 000246494100006

• Magnetic resonance-guided high-intensity ultrasound ablation of the prostate. Topics in magnetic resonance imaging Pauly, K. B., Diederich, C. J., Rieke, V., Bouley, D., Chen, J., Nau, W. H., Ross, A. B., Kinsey, A. M., Sommer, G. 2006; 17 (3): 195-207

  Abstract

  This paper describes our work in developing techniques and devices for magnetic resonance (MR)-guided high-intensity ultrasound ablation of the prostate and includes review of relevant literature.Catheter-based high-intensity ultrasound applicators, in interstitial and transurethral configurations, were developed to be used under MR guidance. Magnetic resonance thermometry and the relevant characteristics and artifacts were evaluated during in vivo thermal ablation of the prostate in 10 animals. Contrast-enhanced MR imaging (MRI) and diffusion-weighted MRI were used to assess tissue damage and compared with histology.During evaluation of these applicators, MR thermometry was used to monitor the temperature distributions in the prostate in real time. Magnetic resonance-derived maximum temperature thresholds of 52 degrees C and thermal dose thresholds of 240 minutes were used to control the extent of treatment and qualitatively correlated well with posttreatment imaging studies and histology. The directional transurethral devices are selective in their ability to target well-defined regions of the prostate gland and can be rotated in discrete steps to conform treatment to prescribed boundaries. The curvilinear applicator is the most precise of these directional techniques. Multisectored transurethral applicators, with dynamic angular control of heating and no rotation requirements, offer a fast and less complex means of treatment with less selective contouring.The catheter-based ultrasound devices can produce spatially selective regions of thermal destruction in prostate. The MR thermal imaging and thermal dose maps, obtained in multiple slices through the target volume, are useful for controlling therapy delivery (rotation, power levels, duration). Contrast-enhanced T1-weighted MRI and diffusion-weighted imaging are useful tools for assessing treatment.

  View details for PubMedID 17414077

• Multisectored interstitial ultrasound applicators for dynamic angular control of thermal therapy MEDICAL PHYSICS Kinsey, A. M., Diederich, C. J., Tyreus, P. D., Nau, W. H., Rieke, V., Pauly, K. B. 2006; 33 (5): 1352-1363

  Abstract

  Dynamic angular control of thermal ablation and hyperthermia therapy with current interstitial heating technology is limited in capability, and often relies upon nonadjustable angular power deposition patterns and/or mechanical manipulation of the heating device. The objective of this study was to investigate the potential of multisectored tubular interstitial ultrasound devices to provide control of the angular heating distribution without device manipulation. Multisectored tubular transducers with independent sector power control were incorporated into modified versions of internally cooled (1.9 mm OD) and catheter-cooled (2.4 mm OD) interstitial ultrasound applicators in this work. The heating capabilities of these multisectored devices were evaluated by measurements of acoustic output properties, measurements of thermal lesions produced in ex vivo tissue samples, biothermal simulations of thermal ablation and hyperthermia treatments, and MR temperature imaging of ex vivo and in vivo experiments. Acoustic beam measurements of each applicator type displayed a 35 degrees -40 degrees acoustic dead zone between each independent sector, with negligible mechanical or electrical coupling. Thermal lesions produced in ex vivo liver tissue with one, two, or three sectors activated ranged from 13-18 mm in radius with contiguous zones of coagulation between active sectors. The simulations demonstrated the degree of angular control possible by using variable power levels applied to each sector, variable duration of applied constant power to individual sectors, respectively, or a multipoint temperature controller to vary the power applied to each sector. Despite the acoustic dead zone between sectors, the simulations also showed that the variance from the maximum lesion radius with three elements activated is within 4%-13% for tissue perfusions from 1-10 kg m(-3) s(-1). Simulations of hyperthermia with maximum tissue temperatures of 45 degrees C and 48 degrees C displayed radial penetration up to 2 cm of the 40 degrees C steady-state contour. Thermal characterizations of trisectored applicators in ex vivo and in vivo muscle, using real-time MR thermal imaging, reinforced angular controllability and negligible radial variance of the heating pattern from the applicators, demonstrated effective heating penetration, and displayed MR compatibility. The multisectored interstitial ultrasound applicators developed in this study demonstrated a significant degree of dynamic angular control of a heating pattern without device manipulation, while maintaining heat penetration consistent with previously reported results from other interstitial ultrasound applicators.

  View details for DOI 10.1118/1.2184443

  View details for Web of Science ID 000237673600019

  View details for PubMedID 16752571

• In vivo porcine liver radiofrequency ablation with simultaneous MR temperature imaging 11th Annual Meeting of the International-Society-for-Magnetic-Resonance-in-Medicine Vigen, K. K., Jarrard, J., Rieke, V., Frisoli, J., Daniel, B. L., Pauly, K. B. JOHN WILEY & SONS INC. 2006: 578–84

  Abstract

  To demonstrate in vivo MR-guided temperature mapping during radiofrequency (RF) ablation of the liver with a commercially available RF generator modified to allow simultaneous RF treatment and MRI.A commercial RF generator was modified using passive filtering to allow the continuous application of the treatment current during MRI studies. A total of six ablations were performed with the device in vivo in three porcine livers, and imaging was concurrently performed using one of two different temperature mapping strategies.MR images acquired during RF ablation demonstrated no noticeable interference from the RF ablation device, which was operated at clinically relevant power levels. Temperature maps showed areas of heating that were consistent with the dimensions of the RF ablation probe, with some asymmetry (likely depending on the orientation of the probe and heat propagation effects), and some differences in heating-spot area stability depending on the specific temperature mapping strategy used. Lesions were visualized on post-ablation imaging and sectioning.The feasibility of performing RF ablation with a modified commercial RF generator simultaneously with MRI was demonstrated. Interference-free MR temperature maps were produced with both variable respiratory motion and mechanical ventilation, and showed the extent of heating as the ablation progressed.

  View details for DOI 10.1002/jmri.20528

  View details for Web of Science ID 000236577000022

  View details for PubMedID 16508928

• Investigation of proton density for measuring tissue temperature JOURNAL OF MAGNETIC RESONANCE IMAGING Chen, J., Daniel, B. L., Pauly, K. B. 2006; 23 (3): 430-437

  Abstract

  To examine the temperature dependence of the proton density (PD) in both adipose and muscle tissues, and the application of the PD as a thermometry parameter in breast tissues.Porcine fat samples and bovine muscle samples were successively heated to temperatures ranging from 30 degrees C to 76 degrees C and then cooled. They were then imaged with a dual-echo spin-echo sequence. T1 and T2 effects were carefully corrected from the images. The apparent PD (APD) in regions of interest (ROIs) and the sum of the APD in all pixels (Sum_APD) were measured and analyzed by linear regression.APD in adipose tissue is linear and reversible, and changes with a 0.3%/ degrees C to 0.45%/ degrees C temperature variation. The temperature coefficient of Sum_APD in adipose tissue is approximately 0.29%/ degrees C, as predicted from the Boltzmann distribution. However, the results in muscle tissue are more variable. There is an offset in both APD and Sum_APD between heating and cooling phases, as well as different temperature coefficients between these two phases.The Sum_APD in adipose tissue validates the 1/T dependence on temperature. The APD is a potentially useful parameter for fat thermometry; however, its application in muscle tissue requires further investigation.

  View details for DOI 10.1002/jmri.20516

  View details for PubMedID 16463298

• Assessment of MR thermometry during high intensity ultrasound ablation of the canine prostate 5th International Symposium on Therapeutic Ultrasound Pauly, K. B., Rieke, V., Pisani, L., Sommer, G., Bouley, D., Diederich, C., Ross, A., Nau, W., Kinsey, A., Dumoulin, C., Watkins, R. AMER INST PHYSICS. 2006: 76–80

  View details for Web of Science ID 000238329700015

• Referenceless MR thermometry during canine prostate ablation 5th International Symposium on Therapeutic Ultrasound Rieke, V., Ross, A. B., Kinsey, A. M., Nau, W. H., Diederich, C. J., Sommer, G., Pauly, K. B. AMER INST PHYSICS. 2006: 91–95

  View details for Web of Science ID 000238329700018

• Dynamic angular control of thermal therapy with stationary multi-sectored tubular ultrasound applicators under MR temperature monitoring 5th International Symposium on Therapeutic Ultrasound Kinsey, A. M., Diederich, C. J., Nau, W. H., Ross, A. B., Pauly, K. B., Rieke, V., Sommer, G. AMER INST PHYSICS. 2006: 455–459

  View details for Web of Science ID 000238329700090

• Targeted prostate thermal therapy with catheter-based ultrasound devices and MR thermal monitoring 5th International Symposium on Therapeutic Ultrasound Diederich, C., Ross, A., Kinsey, A., Nau, W. H., Rieke, V., Pauly, K. B., Sommer, G. AMER INST PHYSICS. 2006: 370–374

  View details for Web of Science ID 000238329700073

• CAPACITIVE MICROMACHINED ULTRASONIC TRANSDUCERS FOR HIGH INTENSITY FOCUSED ABLATION OF UPPER ABDOMINAL TUMORS IEEE Ultrasonics Symposium Wong, S. H., Ergun, A. S., Yaralioglu, G. G., Kupnik, M., Zhuang, X., Oralkan, O., Butts-Pauly, K., Khuri-Yakub, B. T. IEEE. 2006: 841–844

  View details for Web of Science ID 000260407800202

• Truly hybrid x-ray/MR imaging: Toward a streamlined clinical system 5th International Interventional MRI Symposium Ganguly, A., Wen, Z. F., Daniel, B. L., Butts, K., Kee, S. T., Rieke, V., Do, H. M., Pelc, N. J., Alley, M. T., Fahrig, R. ELSEVIER SCIENCE INC. 2005: 1167–77

  Abstract

  We have installed an improved X-ray/MR (XMR) truly hybrid system with higher imaging signal-to-noise ratio (SNR) and versatility than our first prototype. In our XMR design, a fixed anode X-ray fluoroscopy system is positioned between the two donut-shaped magnetic poles of a 0.5T GE Signa-SP magnet (SP-XMR). This paper describes the methods for increased compatibility between the upgraded x-ray and MR systems that have helped improve patient management.A GE OEC 9800 system (GE OEC Salt Lake City, UT) was specially reconfigured for permitting X-ray fluoroscopy inside the interventional magnet. A higher power X-ray tube, a new permanent tube mounting system, automatic exposure control (AEC), remote controlled collimators, choice of multiple frame rates, DICOM image compatibility, magnetically shimmed X-ray detector, X-ray compatible MR coil, and better RF shielding are the highlights of the new system. A total of 23 clinical procedures have been conducted with SP-XMR guidance of which five were performed using the new system.The 70% increased power for fluoroscopy, and a new 6 times higher power single frame imaging mode, has improved imaging capability. The choice of multiple imaging frame rates, AEC, and collimator control allow reduction in X-ray exposure to the patient. The DICOM formatting has permitted easy transfer of clinical images over the hospital PACS network. The increased MR compatibility of the detector and the X-ray transparent MR coil has enabled faster switching between X-ray and MR imaging modes.The improvements introduced in our SP-XMR system have further streamlined X-ray/MR hybrid imaging. Additional clinical procedures could benefit from the new SP-XMR imaging.

  View details for DOI 10.1016/j.acra.2005.03.076

  View details for PubMedID 16099685

• In vivo MR thermometry of frozen tissue using R2* and signal intensity 5th International Interventional MRI Symposium Wansapura, J. P., Daniel, B. L., Vigen, K. K., Butts, K. ELSEVIER SCIENCE INC. 2005: 1080–84

  Abstract

  Cryoablation is one of several minimally invasive treatments that may be suitable for a targeted treatment of prostate cancer. Because efficacy is improved when a sufficiently cold end temperature is reached, the purpose of this work was to demonstrate an image-based thermometry method that could provide temperature maps throughout the frozen tissue. In five in vivo canine prostate cryoablation experiments performed under magnetic resonance imaging guidance, two MR parameters were measured and correlated to temperature: R2* and changes in signal intensity. R2* is elevated approximately linearly as tissue temperature decreases below the freezing point, while the signal intensity decreases exponentially. In vivo temperature maps with isotherms at -5 degrees C, -15 degrees C, and -30 degrees C are demonstrated.

  View details for DOI 10.1016/j.acra.2005.06.006

  View details for PubMedID 16112510

• Effects of spatial and temporal resolution for MR image-guided thermal ablation of prostate with transurethral ultrasound JOURNAL OF MAGNETIC RESONANCE IMAGING Pisani, L. J., Ross, A. B., Diederich, C. J., Nau, W. H., Sommer, F. G., Glover, G. H., Butts, K. 2005; 22 (1): 109-118

  Abstract

  To describe approaches for determining optimal spatial and temporal resolutions for the proton resonance frequency shift method of quantitative magnetic resonance temperature imaging (MRTI) guidance of transurethral ultrasonic prostate ablation.Temperature distributions of two transurethral ultrasound applicators (90 degrees sectored tubular and planar arrays) for canine prostate ablation were measured via MRTI during in vivo sonication, and agree well with two-dimensional finite difference model simulations at various spatial resolutions. Measured temperature distributions establish the relevant signal-to-noise ratio (SNR) range for thermometry in an interventional MR scanner, and are reconstructed at different resolutions to compare resultant temperature measurements. Various temporal resolutions are calculated by averaging MRTI frames.When noise is added to simulated temperature distributions for tubular and planar applicators, the minimum root mean squared (RMS) error is achieved by reconstructing to pixel sizes of 1.9 and 1.7 mm, respectively. In in vivo measurements, low spatial resolution MRTI data are shown to reduce the noise without significantly affecting thermal dose calculations. Temporal resolution of 0.66 frames/minute leads to measurement errors of more than 12 degrees C during rapid heating.Optimizing MRTI pixel size entails balancing large pixel SNR gain with accuracy in representing underlying temperature distributions.

  View details for DOI 10.1002/jmri.20339

  View details for PubMedID 15971190

• X-ray compatible radiofrequency coil for magnetic resonance imaging MAGNETIC RESONANCE IN MEDICINE Rieke, V., GANGULY, A., Daniel, B. L., Scott, G., Pauly, J. M., Fahrig, R., Pelc, N. J., Butts, K. 2005; 53 (6): 1409-1414

  Abstract

  The range of RF coils that can be used in combined X-ray/MR (XMR) systems is limited because many conventional coils contain highly X-ray attenuating materials that are visible in the X-ray images and potentially obscure patient anatomy. In this study, an X-ray compatible coil design that has minimal X-ray attenuation in the field of view (FOV) of the X-ray image is presented. In this design, aluminum is used for the loop conductor and discrete elements of the coil are eliminated from the X-ray FOV. A surface coil and an abdominal phased array coil were built using the X-ray compatible design. X-ray attenuation and MR imaging properties of the coils were evaluated and compared to conventional coils. The X-ray compatible phased array coil was used to image patients during two interventional procedures in the XMR system. The X-ray compatible coils allowed for fluoroscopic X-ray image acquisition, without degradation by the coil, while maintaining excellent MR imaging qualities.

  View details for DOI 10.1002/mrm.20494

  View details for PubMedID 15906285

• Curvilinear transurethral ultrasound applicator for selective prostate thermal therapy MEDICAL PHYSICS Ross, A. B., Diederich, C. J., Nau, W. H., Rieke, V., Butts, R. K., Sommer, G., Gill, H., Bouley, D. M. 2005; 32 (6): 1555-1565

  Abstract

  Thermal therapy offers a minimally invasive option for treating benign prostatic hyperplasia (BPH) and localized prostate cancer. In this study we investigated a transurethral ultrasound applicator design utilizing curvilinear, or slightly focused, transducers to heat prostatic tissue rapidly and controllably. The applicator was constructed with two independently powered transducer segments operating at 6.5 MHz and measuring 3.5 mm x 10 mm with a 15 mm radius of curvature across the short axis. The curvilinear applicator was characterized by acoustic efficiency measurements, acoustic beam plots, biothermal simulations of human prostate, ex vivo heating trials in bovine liver, and in vivo heating trials in canine prostate (n=3). Each transducer segment was found to emit a narrow acoustic beam (max width <3 mm), which extended the length of the transducer, with deeper penetration than previously developed planar or sectored tubular transurethral ultrasound applicators. Acoustic and biothermal simulations of human prostate demonstrated three treatment schemes for the curvilinear applicator: single shot (10 W, 60 s) schemes to generate narrow ablation zones (13 x 4 mm, 52 degrees C at the lesion boundary), incremental rotation (10 W, 10 degrees/45 s) to generate larger sector-shaped ablation zones (16 mm x 180 degrees sector), and rotation with variable sonication times (10 W, 10 degrees/15-90 s) to conform the ablation zone to a predefined boundary (9-17 mm x 180 degrees sector, 13 min total treatment time). During in vivo canine prostate experiments, guided by MR temperature imaging, single shot sonications (6 W/transducer, 2-3 min) with the curvilinear applicator ablated 20 degree sections of tissue to the prostate boundary (9-15 mm). Multiple adjacent sonications ("sweeping") ablated large sections of the prostate (180 degrees) by using the MR temperature imaging to adjust the power (4-6.4 W/transducer) and sonication time (30-180 s) at each 10 degrees rotation such that the periphery of the prostate reached 52 degrees C before the next rotation. The conclusion of this study was that the curvilinear applicator produces a narrow and penetrating ultrasound beam that, when combined with image guidance, can provide a precise technique for ablating target regions with a contoured outer boundary, such as the prostate capsule, by rotating in small steps while dynamically adjusting the net applied electrical power and sonication time at each position.

  View details for DOI 10.1118/1.1924314

  View details for Web of Science ID 000229908600015

  View details for PubMedID 16013714

• MRI-guided interstitial ultrasound thermal therapy of the prostate: A feasibility study in the canine model MEDICAL PHYSICS Nau, W. H., Diederich, C. J., Ross, A. B., Butts, K., Rieke, V., Bouley, D. M., Gill, H., Daniel, B., Sommer, G. 2005; 32 (3): 733-743

  Abstract

  The feasibility of MRI-guided interstitial ultrasound thermal therapy of the prostate was evaluated in an in vivo canine prostate model. MRI compatible, multielement interstitial ultrasound applicators were developed using 1.5 mm diameter cylindrical piezoceramic transducers (7 to 8 MHz) sectored to provide 180 degrees of angular directional heating. Two in vivo experiments were performed in canine prostate. The first using two interstitial ultrasound applicators, the second using three ultrasound applicators in conjunction with rectal and urethral cooling. In both experiments, the applicators were inserted transperineally into the prostate with the energy directed ventrally, away from the rectum. Electrical power levels of 5-17 W per element (approximately 1.6-5.4 W acoustic output power) were applied for heating periods of 18 and 48 min. Phase-sensitive gradient-echo MR imaging was used to monitor the thermal treatment in real-time on a 0.5 T interventional MRI system. Contrast-enhanced T1-weighted images and vital-stained serial tissue sections were obtained to assess thermal damage and correlate to real-time thermal contour plots and calculated thermal doses. Results from these studies indicated a large volume of ablated (nonstained) tissue within the prostate, extending 1.2 to 2.0 cm from the applicators to the periphery of the gland, with the dorsal margin of coagulation well-defined by the applicator placement and directionality. The shape of the lesions correlated well to the hypointense regions visible in the contrast-enhanced T1-weighted images, and were also in good agreement with the contours of the 52 degrees C threshold temperature and t43 > 240 min. This study demonstrates the feasibility of using directional interstitial ultrasound in conjunction with MRI thermal imaging to monitor and possibly control thermal coagulation within a targeted tissue volume while potentially protecting surrounding tissue, such as rectum, from thermal damage.

  View details for DOI 10.1118/1.1861163

  View details for Web of Science ID 000227910600010

  View details for PubMedID 15839345

• Reduction of blurring in view angle tilting MRI MAGNETIC RESONANCE IN MEDICINE Butts, K., Pauly, J. M., Gold, G. E. 2005; 53 (2): 418-424

  Abstract

  Magnetic resonance imaging (MRI) in the presence of metallic objects suffers from slice-selection errors and in-plane distortions. View angle tilting (VAT) corrects for in-plane distortions by adding a gradient on the slice-select axis during readout, but can suffer from image blurring. This work demonstrates that the major source of blurring is a slice profile modulation of the data, and proposes several solutions to prevent such blurring. Multiple high-bandwidth readouts are demonstrated to reduce the blurring while improving the signal-to-noise ratio (SNR) over a single high-bandwidth readout.

  View details for DOI 10.1002/mrm.20375

  View details for Web of Science ID 000226651100020

  View details for PubMedID 15678535

• MR-guided transjugular intrahepatic portosystemic shunt creation with use of a hybrid radiography/MR system 29th Annual Meeting of the Society-of-Interventional-Radiology (SIR) Kee, S. T., GANGULY, A., Daniel, B. L., Wen, Z. F., Butts, K., Shimikawa, A., Pelc, N. J., Fahrig, R., Dake, M. D. ELSEVIER SCIENCE INC. 2005: 227–34

  Abstract

  To evaluate the performance of a combined hybrid radiography/magnetic resonance (MR) unit to guide portal vein (PV) puncture during human transjugular intrahepatic portosystemic shunt (TIPS) creation.Fourteen patients undergoing TIPS creation were studied during standard clinical applications. Patients were anesthetized and then positioned in an open MR unit containing a flat-panel radiographic fluoroscopic unit. With use of a combination of fluoroscopy and MR imaging, the PV was accessed and the TIPS procedure was performed. A noncovered nitinol stent or a covered stent-graft was placed in the TIPS tract. Number of punctures required, total procedure time, fluoroscopy time, procedural success rate, complications, and ultrasonographic and clinical follow-up were recorded.Clinical success was obtained in 13 of 14 patients. In one patient, extrahepatic puncture of the PV occurred, resulting in hemorrhage and requiring placement of a covered stent to control the bleeding. The mean number of punctures required to access the PV was 2.6 +/- 1.7, and the total procedure time was 2.5 hours +/- 0.6. Mean fluoroscopy time was 22.3 minutes +/- 5.5. Results of clinical and ultrasonographic follow-up compare favorably to previously published reports.TIPS creation with a combination hybrid radiography/MR unit is feasible and may reduce the number of needle passes required and radiation exposure, with similar overall outcomes compared with studies reported in the literature.

  View details for DOI 10.1097/01.RVI.0000143766.08029.6E

  View details for PubMedID 15713923

• Biothermal modeling of transurethral ultrasound applicators for MR-guided prostate thermal therapy Conference on Treatment of Tissue: Energy Delivery and Assessment III Ross, A. B., Diederich, C. J., Nau, W. H., Tyreus, D., Gill, H., Bouley, D., Butts, R. K., Rieke, V., Daniel, B., Sommer, G. SPIE-INT SOC OPTICAL ENGINEERING. 2005: 220–227

  View details for DOI 10.1117/12.592491

  View details for Web of Science ID 000229738000020

• The effect of axial loading and spine position on intervertebral disc hydration: An in vivo pilot study JOURNAL OF BACK AND MUSCULOSKELETAL REHABILITATION Lee, S. U., Fredericson, M., Butts, K., Lang, P. 2005; 18 (1-2): 15-20

  View details for Web of Science ID 000232937000003

• Catheter-based ultrasound applicators for selective thermal ablation: progress towards MRI-guided applications in prostate INTERNATIONAL JOURNAL OF HYPERTHERMIA Diederich, C. J., Nau, W. H., Ross, A. B., Tyreus, P. D., Butts, K., Rieke, V., Sommer, G. 2004; 20 (7): 739-756

  Abstract

  High-temperature thermal therapy is emerging as a feasible treatment option for prostate cancer and benign prostatic hyperplasia. Previous investigations have demonstrated distinct advantages of catheter-based ultrasound technology over other heating modalities for thermal ablation therapies, with significant potential for better spatial control and faster heating times. The purpose of this study was to develop ultrasound devices and techniques specifically for treating prostate cancer in conjunction with magnetic resonance thermal imaging (MRTI) to monitor and control treatment progression. Directional transurethral applicators have been designed with arrays of sectored tubular (90 degrees active acoustic sector) or with narrow planar transducer segments and integrated with a flexible delivery catheter with a cooling balloon. This applicator can be rotated within the prostatic urethra to target specific regions during treatment. MRI compatible catheter-cooled interstitial ultrasound applicators with 180 degrees active acoustic sectors were developed specifically to treat the prostate. These applicators may be implanted through the perineum into the posterior portion of the prostate, with their heating energy directed away from the rectum. Both heating strategies were evaluated via biothermal simulations and in vivo experiments within canine prostate (n = 3). During the in vivo studies, MRTI was used to monitor treatment temperatures, cytotoxic thermal doses (t43 > 240 min) and corresponding maximum temperature thresholds (Tmax > 52 degrees C) within three imaging planes simultaneously. Urethral and endorectal cooling was employed with both treatment strategies to provide further protection of the urethral mucosa and rectum from thermal damage. Results using the transurethral applicators demonstrated that narrow zones of coagulation (approximately 30 degrees sector for planar, approximately 90 degrees for tubular), extending up to 20 mm from the urethra to the periphery of the prostate gland, could be produced within 10-15 min. Further, rotation of the applicator during treatment could be used to destroy larger regions in the prostate. Experiments using multiple interstitial directional applicators (approximately 180 degrees active sectors), implanted within the posterior margin of the prostate with the energy directed away from the rectum, produced contiguous zones of thermal coagulation which extended from the posterior prostate toward the anterior-lateral periphery of the gland. Both transurethral and interstitial treatment strategies demonstrated significant potential for thermal ablation of localized prostate cancer, particularly when MRTI is used to guide and assess treatment.

  View details for DOI 10.1080/02656730410001721816

  View details for Web of Science ID 000225135100006

  View details for PubMedID 15675669

• Referenceless PRF shift thermometry MAGNETIC RESONANCE IN MEDICINE Rieke, V., Vigen, K. K., Sommer, G., Daniel, B. L., Pauly, J. M., Butts, K. 2004; 51 (6): 1223-1231

  Abstract

  The proton resonance frequency (PRF) shift provides a means of measuring temperature changes during minimally invasive thermotherapy. However, conventional PRF thermometry relies on the subtraction of baseline images, which makes it sensitive to tissue motion and frequency drift during the course of treatment. In this study, a new method is presented that eliminates these problems by estimating the background phase from each acquired image phase. In this referenceless method, a polynomial is fit to the background phase outside the heated region in a weighted least-squares fit. Extrapolation of the polynomial to the heated region serves as the background phase estimate, which is then subtracted from the actual phase. The referenceless method is demonstrated on a phantom during laser heating, 0 degrees temperature rise images of in vivo human liver, interstitial laser ablation of porcine liver, and transurethral ultrasound ablation of canine prostate. A good correlation between temperature maps reconstructed with the referenceless and subtraction methods was found.

  View details for DOI 10.1002/mrm.20090

  View details for PubMedID 15170843

• Highly directional transurethral ultrasound applicators with rotational control for MRI-guided prostatic thermal therapy PHYSICS IN MEDICINE AND BIOLOGY Ross, A. B., Diederich, C. J., Nau, W. H., Gill, H., Bouley, D. M., Daniel, B., Rieke, V., Butts, R. K., Sommer, G. 2004; 49 (2): 189-204

  Abstract

  Transurethral ultrasound applicators with highly directional energy deposition and rotational control were investigated for precise treatment of benign prostatic hyperplasia (BPH) and adenocarcinoma of the prostate (CaP). Two types of catheter-based applicators were fabricated, using either 90 degrees sectored tubular (3.5 mm OD x 10 mm) or planar transducers (3.5 mm x 10 mm). They were constructed to be MRI compatible, minimally invasive and allow for manual rotation of the transducer array within a 10 mm cooling balloon. In vivo evaluations of the applicators were performed in canine prostates (n = 3) using MRI guidance (0.5 T interventional magnet). MR temperature imaging (MRTI) utilizing the proton resonance frequency shift method was used to acquire multiple-slice temperature overlays in real time for monitoring and guiding the thermal treatments. Post-treatment T1-weighted contrast-enhanced imaging and triphenyl tetrazolium chloride stained tissue sections were used to define regions of tissue coagulation. Single sonications with the 90 degrees tubular applicator (9-15 W, 12 min, 8 MHz) produced coagulated zones covering an 80 degrees wedge of the prostate extending from 1-2 mm outside the urethra to the outer boundary of the gland (16 mm radial coagulation). Single sonications with the planar applicator (15-20 W, 10 min, approximately 8 MHz) generated thermal lesions of approximately 30 degrees extending to the prostate boundary. Multiple sequential sonications (sweeping) of a planar applicator (12 W with eight rotations of 30 degrees each) demonstrated controllable coagulation of a 270 degrees contiguous section of the prostate extending to the capsule boundary. The feasibility of using highly directional transurethral ultrasound applicators with rotational capabilities to selectively coagulate regions of the prostate while monitoring and controlling the treatments with MRTI was demonstrated in this study.

  View details for DOI 10.1088/0031-9155/49/2/0020

  View details for Web of Science ID 000220421700002

  View details for PubMedID 15083666

• MRI-temperature mapping during ultrasound prostate ablation using fat for phase estimation. Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference Rieke, V., Ross, A. B., Nau, W. H., Diederich, C. J., Sommer, G., Butts, K. 2004; 4: 2500-2502

  Abstract

  Referenceless proton resonance frequency (PRF) shift thermometry provides a means to measure temperature changes during minimally invasive thermotherapy that is inherently robust to motion and tissue displacement. In this study, the method is expanded to allow background phase estimation from fatty tissue. A correction scheme for temperature map distortions caused by the ultrasound applicator is developed. The method is tested during thermal ablation of canine prostate using a directional transurethral ultrasound applicator.

  View details for PubMedID 17270780

• MRI-temperature mapping during ultrasound prostate ablation using fat for phase estimation PROCEEDINGS OF THE 26TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-7 Rieke, V., Ross, A. B., Nau, W. H., Diederich, C. J., Sommer, G., Butts, K. 2004; 26: 2500-2502

  Abstract

  Referenceless proton resonance frequency (PRF) shift thermometry provides a means to measure temperature changes during minimally invasive thermotherapy that is inherently robust to motion and tissue displacement. In this study, the method is expanded to allow background phase estimation from fatty tissue. A correction scheme for temperature map distortions caused by the ultrasound applicator is developed. The method is tested during thermal ablation of canine prostate using a directional transurethral ultrasound applicator.

  View details for Web of Science ID 000225461800646

• Triggered, navigated, multi-baseline method for proton resonance frequency temperature mapping with respiratory motion MAGNETIC RESONANCE IN MEDICINE Vigen, K. K., Daniel, B. L., Pauly, J. M., Butts, K. 2003; 50 (5): 1003-1010

  Abstract

  A technique is presented for the acquisition of temperature maps in the presence of variable respiratory motion using the proton resonance frequency (PRF) shift. The technique uses respiratory triggering, diaphragm position determination with a navigator echo, and the collection of multiple baseline images to generate temperature maps. Laser ablations were performed in an ex vivo liver phantom undergoing variable simulated respiratory motion and in vivo in four porcine livers, demonstrating a reduction of artifacts in the computed temperature maps compared with conventional single baseline techniques, both uncorrected and corrected for motion.

  View details for DOI 10.1002/mrm.10608

  View details for PubMedID 14587011

• First use of a truly-hybrid X-ray/MR imaging system for guidance of brain biopsy ACTA NEUROCHIRURGICA Fahrig, R., Heit, G., Wen, Z., Daniel, B. L., Butts, K., Pelc, N. J. 2003; 145 (11): 995-997

  Abstract

  The use of a new hybrid imaging system for guidance of a brain biopsy is described. The system combines the strengths of MRI (soft-tissue contrast, arbitrary plane selection) with those of x-ray fluoroscopy (high-resolution real-time projection images, clear portrayal of bony structures) and allows switching between the imaging modalities without moving the patient. The biopsy was carried out using x-ray guidance for direction of the needle through the foramen ovale and MR guidance to target the soft-tissue lesion. Appropriate samples were acquired. The system could be particularly effective for guidance of those cases where motion, swelling, resection and other intra-operative anatomical changes cannot be accounted for using traditional stereotactic-based imaging approaches.

  View details for DOI 10.1007/s00701-003-0138-7

  View details for Web of Science ID 000186686300020

  View details for PubMedID 14628205

• Pair of resonant fiducial markers for localization of endovascular catheters at all catheter orientations JOURNAL OF MAGNETIC RESONANCE IMAGING Kuehne, T., Fahrig, R., Butts, K. 2003; 17 (5): 620-624

  Abstract

  To test wireless resonance circuits (RC) to be used as fiducial marker of endovascular catheters during MR-guided interventions. Current markers loose their signal enhancement for certain catheter orientations. The purpose of this study was to test a marker setup which overcomes this orientation problem.The markers were constructed from a pair of two RCs. The RCs were individually tuned and the coil axes were oriented perpendicular to each other in order to decouple the two RCs. The markers were mounted on the tip of endovascular catheters and tested in vitro and in one porcine in vivo experiment.An intense MR signal at similar signal levels was noted at all catheter orientations. In the in vivo experiment the markers allowed for fast and reliable MR guidance of the catheters.A pair of two individually tuned and decoupled RCs is well suited for MR guidance of endovascular catheters.

  View details for DOI 10.1002/jmri.10307

  View details for Web of Science ID 000182630800015

  View details for PubMedID 12720274

• Diffusion-weighted MRI after cryosurgery of the canine prostate. Magnetic resonance imaging. Journal of magnetic resonance imaging : JMRI Butts, K., Daniel, B. L., Chen, L., Bouley, D. M., Wansapura, J., Maier, S. E., Dumoulin, C., Watkins, R. 2003; 17 (1): 131-135

  Abstract

  To evaluate the acute lesion created by cryosurgery with diffusion-weighted magnetic resonance imaging (DWI).The appearance of the acute cryolesion was evaluated in four canine prostates DWI after they were warmed to original body temperature. The prostates were excised, stained with triphenyl tetrazolium chloride (TTC), photographed, prepared for hematoxylin and eosin (H&E) staining, and examined under a light microscope.A marked decrease in apparent diffusion coefficient of 38% was evident in the center of the previously frozen tissue, but not in all of the previously frozen tissue. Histologic results confirm differences between the iceball core and the periphery of the iceball, which have markedly different imaging characteristics on DWI.The core of the previously frozen tissue has a reduced apparent diffusion coefficient (ADC) compared to the periphery of the previously frozen tissue and previously unfrozen tissue.

  View details for PubMedID 12500282

• Diffusion-weighted MRI after cryosurgery of the canine prostate JOURNAL OF MAGNETIC RESONANCE IMAGING Butts, K., Daniel, B. L., Chen, L. L., Bouley, D. M., Wansapura, J., Maier, S. E., Dumoulin, C., Watkins, R. 2003; 17 (1): 131-135

  Abstract

  To evaluate the acute lesion created by cryosurgery with diffusion-weighted magnetic resonance imaging (DWI).The appearance of the acute cryolesion was evaluated in four canine prostates DWI after they were warmed to original body temperature. The prostates were excised, stained with triphenyl tetrazolium chloride (TTC), photographed, prepared for hematoxylin and eosin (H&E) staining, and examined under a light microscope.A marked decrease in apparent diffusion coefficient of 38% was evident in the center of the previously frozen tissue, but not in all of the previously frozen tissue. Histologic results confirm differences between the iceball core and the periphery of the iceball, which have markedly different imaging characteristics on DWI.The core of the previously frozen tissue has a reduced apparent diffusion coefficient (ADC) compared to the periphery of the previously frozen tissue and previously unfrozen tissue.

  View details for DOI 10.1002/jmri.10227

  View details for Web of Science ID 000182657900014

• Line scan diffusion imaging of the spine AMERICAN JOURNAL OF NEURORADIOLOGY Bammer, R., Herneth, A. M., Maier, S. E., Butts, K., Prokesch, R. W., Do, H. M., Atlas, S. W., Moseley, M. E. 2003; 24 (1): 5-12

  Abstract

  Recent findings suggest that diffusion-weighted imaging might be an important adjunct to the diagnostic workup of disease processes in the spine, but physiological motion and the challenging magnetic environment make it difficult to perform reliable quantitative diffusion measurements. Multi-section line scan diffusion imaging of the spine was implemented and evaluated to provide quantitative diffusion measurements of vertebral bodies and intervertebral disks.Line scan diffusion imaging of 12 healthy study participants and three patients with benign vertebral compression fractures was performed to assess the potential of line scan diffusion imaging of the spinal column. In a subgroup of six participants, multiple b-value (5-3005 s/mm(2)) images were obtained to test for multi-exponential signal decay.All images were diagnostic and of high quality. Mean diffusion values were (230 +/- 83) x 10(-6) mm(2)/s in the vertebral bodies, (1645 +/- 213) x 10(-6) mm(2)/s in the nuclei pulposi, (837 +/- 318) x 10(-6) mm(2)/s in the annuli fibrosi and ranged from 1019 x 10(-6) mm(2)/s to 1972 x 10(-6) mm(2)/s in benign compression fractures. The mean relative intra-participant variation of mean diffusivity among different vertebral segments (T10-L5) was 2.97%, whereas the relative difference in mean diffusivity among participants was 7.41% (P <.0001). The estimated measurement precision was <2%. A bi-exponential diffusion attenuation was found only in vertebral bodies.Line scan diffusion imaging is a robust and reliable method for imaging the spinal column. It does not suffer as strongly from susceptibility artifacts as does echo-planar imaging and is less susceptible to patient motion than are other multi-shot techniques. The different contributions from the water and fat fractions need to be considered in diffusion-weighted imaging of the vertebral bodies.

  View details for Web of Science ID 000180962400004

  View details for PubMedID 12533319

• Dynamic magnetic resonance guided treatment of developmental dysplasia of the hip JOURNAL OF PEDIATRIC ORTHOPAEDICS-PART B Lincoln, T. L., Vandevenne, J. E., Rinsky, L. A., Butts, K., Lang, P. 2002; 11 (4): 279-283

  Abstract

  This study demonstrates the feasibility and advantages of near real-time, multiplanar, dynamic magnetic resonance image-assisted treatment of patients with developmental dysplasia of the hip. Pathoanatomy and dynamic blocks to reduction are visualized with anatomic clarity not otherwise possible. Continuous imaging allows accurate assessment and maintenance of optimum positioning throughout the casting procedure. Patient charges for this new technique are less than standard methods of treatment, and the child receives no ionizing radiation.

  View details for Web of Science ID 000178875700002

  View details for PubMedID 12370576

• Study of laser ablation in the in vivo rabbit brain with MR thermometry JOURNAL OF MAGNETIC RESONANCE IMAGING Chen, L. L., Wansapura, J. P., Heit, G., Butts, K. 2002; 16 (2): 147-152

  Abstract

  To investigate the peak temperature and thermal dose (T(43)) as tissue damage indicators for thermal therapy.The proton resonant frequency (PRF) shift thermal coefficient was calibrated on six in vivo rabbit brains during interstitial laser ablation. The peak temperature and T(43) were correlated with the lesion boundary observed on T2-weighted spin-echo (SE) MRI at 4 hours post-heating in seven thermal lesions using direct MR measurement and analysis based on a binary discriminate model.The peak temperature and T(43) were 48.3 +/- 1.7 degrees C and 191 +/- 219 minutes, respectively, from the direct MR measurement. The values derived by the binary discriminate analysis were 47.8 +/- 2.2 degrees C and 28 +/- 41 minutes, respectively.Our results suggest that tissue damage in rabbit brain 4 hours after thermal ablation can be predicted reliably from a threshold temperature of approximately 48 degrees C.

  View details for DOI 10.1002/jmri.10152

  View details for PubMedID 12203761

• Truly hybrid interventional MR/x-ray system: Investigation of in vivo applications ACADEMIC RADIOLOGY Fahrig, R., Butts, K., Wen, Z. F., Saunders, R., Kee, S. T., Sze, D. Y., Daniel, B. L., Laerum, F., Pelc, N. J. 2001; 8 (12): 1200-1207

  Abstract

  The purpose of this study was to provide in vivo demonstrations of the functionality of a truly hybrid interventional x-ray/magnetic resonance (MR) system.A digital flat-panel x-ray system (1,024(2) array of 200 microm pixels, 30 frames per second) was integrated into an interventional 0.5-T magnet. The hybrid system is capable of MR and x-ray imaging of the same field of view without patient movement. Two intravascular procedures were performed in a 22-kg porcine model: placement of a transjugular intrahepatic portosystemic shunt (TIPS) (x-ray-guided catheterization of the hepatic vein, MR fluoroscopy-guided portal puncture, and x-ray-guided stent placement) and mock chemoembolization (x-ray-guided subselective catheterization of a renal artery branch and MR evaluation of perfused volume).The resolution and frame rate of the x-ray fluoroscopy images were sufficient to visualize and place devices, including nitinol guidewires (0.016-0.035-inch diameter) and stents and a 2.3-F catheter. Fifth-order branches of the renal artery could be seen. The quality of both real-time (3.5 frames per second) and standard MR images was not affected by the x-ray system. During MR-guided TIPS placement, the trocar and the portal vein could be easily visualized, allowing successful puncture from hepatic to portal vein.Switching back and forth between x-ray and MR imaging modalities without requiring movement of the patient was demonstrated. The integrated nature of the system could be especially beneficial when x-ray and MR image guidance are used iteratively.

  View details for Web of Science ID 000172759200002

  View details for PubMedID 11770916

• Temperature mapping of frozen tissue using eddy current compensated half excitation RF pulses MAGNETIC RESONANCE IN MEDICINE Wansapura, J. P., Daniel, B. L., Pauly, J., Butts, K. 2001; 46 (5): 985-992

  Abstract

  Cryosurgery has been shown to be an effective therapy for prostate cancer. Temperature monitoring throughout the cryosurgical iceball could dramatically improve efficacy, since end temperatures of at least -40 degrees C are required. The results of this study indicate that MR thermometry based on tissue R(*)(2) has the potential to provide this information. Frozen tissue appears as a complete signal void on conventional MRI. Ultrashort echo times (TEs), achievable with half pulse excitation and a short spiral readout, allow frozen tissue to be imaged and MR characteristics to be measured. However, half pulse excitation is highly sensitive to eddy current distortions of the slice-select gradient. In this work, the effects of eddy currents on the half pulse technique are characterized and methods to overcome these effects are developed. The methods include: 1) eddy current compensated slice-select gradients, and 2) a correction for the phase shift between the first and second half excitations at the center of the slice. The effectiveness of these methods is demonstrated in R(*)(2) maps calculated within the frozen region during cryoablation.

  View details for PubMedID 11675651

• Freehand iMRI-guided large-gauge core needle biopsy: A new minimally invasive technique for diagnosis of enhancing breast lesions 7th Annual Meeting of the International-Society-for-Magnetic-Resonance-in-Medicine (ISMRM) Daniel, B. L., Birdwell, R. L., Butts, K., Nowels, K. W., Ikeda, D. M., Heiss, S. G., Cooper, C. R., Jeffrey, S. S., Dirbas, F. M., Herfkens, R. J. JOHN WILEY & SONS INC. 2001: 896–902

  Abstract

  The lack of reliable methods for minimally invasive biopsy of suspicious enhancing breast lesions has hindered the utilization of contrast-enhanced magnetic resonance imaging (MRI) for the detection and diagnosis of breast cancer. In this study, a freehand method was developed for large-gauge core needle biopsy (LCNB) guided by intraprocedural MRI (iMRI). Twenty-seven lesions in nineteen patients were biopsied using iMRI-guided LCNB without significant complications. Diagnostic tissue was obtained in all cases. Nineteen of the 27 lesions were subsequently surgically excised. Histopathologic analysis confirmed that iMRI-guided LCNB correctly distinguished benign lesions from malignancy in 18 of the 19 lesions. The histology revealed by core biopsy was partially discrepant with surgical biopsy in 2 of the other 19 lesions. Freehand iMRI-guided LCNB of enhancing breast lesions is promising. Larger studies are needed to determine the smallest lesion that can be sampled reliably and to precisely measure the accuracy of iMRI-guided LCNB as a minimally invasive tool to diagnose suspicious lesions found by breast MRI. J. Magn. Reson. Imaging 2001;13:896-902.

  View details for Web of Science ID 000171296500013

  View details for PubMedID 11382950

• Dynamic MR imaging and stress testing in glenohumeral instability: Comparison with normal shoulders and clinical/surgical findings JOURNAL OF MAGNETIC RESONANCE IMAGING Hodge, D. K., Beaulieu, C. F., Thabit, G. H., Gold, G. E., Bergman, A. G., Butts, R. K., Dillingham, M. F., Herfkens, R. J. 2001; 13 (5): 748-756

  Abstract

  Our objectives were to test the hypotheses that: 1) during shoulder motion, glenohumeral alignment differs between asymptomatic shoulders and those with symptomatic instability; 2) during magnetic resonance (MR)-monitored physical exam or stress testing, glenohumeral alignment differs between asymptomatic shoulders and those with instability; and 3) glenohumeral translation during MR stress testing correlates with findings of shoulder instability by clinical exam and exam under anesthesia (EUA). Using an open-configuration 0.5 T MR imaging (MRI) system, we studied symptomatic shoulders in 11 subjects and compared them to their contralateral asymptomatic shoulders. Each shoulder was studied during abduction/adduction and internal/external rotation to determine the humeral head position on the glenoid. An examiner also performed the MR stress test on each shoulder by applying manual force on the humeral head during imaging. All shoulders were assigned an instability grade from the MR stress test, and this grade was correlated with: 1) clinical exam grade assigned during preoperative assessment by an orthopedic surgeon and 2) intraoperative instability grade by EUA immediately preceding arthroscopy. With dynamic abduction and internal/external rotation, the humeral head remained centered on the glenoid in 9 of 11 shoulders, but in two subjects there were dramatic demonstrations of subluxation. With stress testing, a trend toward more joint laxity was demonstrated in symptomatic than in asymptomatic joints (P = 0.11). MR grading of instability correlated directly with clinical grading in six cases and underestimated the degree of instability relative to clinical exam in the other cases. MR instability grading systematically underestimated instability compared with EUA in 7 of the 10 cases that underwent surgical repair. We concluded that dynamic MR evaluation of glenohumeral alignment did not demonstrate abnormalities in symptomatic shoulders in 8 of 10 patients, whereas 2 patients showed dramatic findings of subluxation. Manual stress testing during dynamic MR examination showed a strong correlation with clinical instability grading. Dynamic shoulder MR examination during stress testing could, with further validation, become a useful adjunct to shoulder instability evaluations. J. Magn. Reson. Imaging 2001;13:748-756.

  View details for Web of Science ID 000171296300012

  View details for PubMedID 11329197

• A truly hybrid interventional MR/X-ray system: Feasibility demonstration 8th Annual Meeting of the ISMRM Fahrig, R., Butts, K., Rowlands, J. A., Saunders, R., Stanton, J., Stevens, G. M., Daniel, B. L., Wen, Z. F., Ergun, D. L., Pelc, N. J. JOHN WILEY & SONS INC. 2001: 294–300

  Abstract

  A system enabling both x-ray fluoroscopy and MRI in a single exam, without requiring patient repositioning, would be a powerful tool for image-guided interventions. We studied the technical issues related to acquisition of x-ray images inside an open MRI system (GE Signa SP). The system includes a flat-panel x-ray detector (GE Medical Systems) placed under the patient bed, a fixed-anode x-ray tube overhead with the anode-cathode axis aligned with the main magnetic field and a high-frequency x-ray generator (Lunar Corp.). New challenges investigated related to: 1) deflection and defocusing of the electron beam of the x-ray tube; 2) proper functioning of the flat panel; 3) effects on B0 field homogeneity; and 4) additional RF noise in the MR images. We have acquired high-quality x-ray and MR images without repositioning the object using our hybrid system, which demonstrates the feasibility of this new configuration. Further work is required to ensure that the highest possible image quality is achieved with both MR and x-ray modalities.

  View details for Web of Science ID 000171295900018

  View details for PubMedID 11169837

• MRI study of immediate cell viability in focused ultrasound lesions in the rabbit brain JOURNAL OF MAGNETIC RESONANCE IMAGING Chen, L., Bouley, D. M., Harris, B. T., Butts, K. 2001; 13 (1): 23-30

  Abstract

  The purpose of this study was to evaluate cell viability in MR imaged focused ultrasound (FUS) lesions using cell-viability staining with triphenyl tetrazolium chloride (TTC) and both light and electron microscopy. Ten paired ultrasonic lesions were created in 5 rabbit brains in vivo with an ultrasound beam of 1.5 MHz electrical power input to the transducer of 50 W and exposure duration of 15 seconds. T2-weighted fast spin-echo (FSE) MRI was performed to detect the FUS lesions in the brain 4 hours after treatment, after which the animals were immediately euthanized. Lesion sizes were measured on TTC-stained specimens, histological sections stained with hematoxylin and eosin (H&E), and T2-weighted MR images. The differences between the lesion diameters measured with the three methods were within the range of 0.1--0.7 mm. The lesion sizes measured from MRI correlated well with those seen from H&E sections. The measurements from MRI slightly overestimated lesion sizes on TTC-stained wet tissues by approximately one MRI pixel (0.31 mm). Electron microscopy demonstrated nuclear and cytoplasmic ultrastructural damage within the grey-white, non-TTC-stained lesion zone, whereas the TTC-stained normal tissue showed preservation of neuronal ultrastructure. Therefore, MR-imaged lesions represent a cell-death zone in rabbit brain 4 hours after FUS ablation, with slight overestimation by approximately one MRI pixel. J. Magn. Reson. Imaging 2001;13:23-30.

  View details for Web of Science ID 000171295800005

  View details for PubMedID 11169799

• Changes in posterior disc bulging and intervertebral foraminal size associated with flexion-extension movement: a comparison between L4-5 and L5-S1 levels in normal subjects. spine journal Fredericson, M., Lee, S. U., Welsh, J., Butts, K., Norbash, A., Carragee, E. J. 2001; 1 (1): 10-17

  Abstract

  No previous study has used magnetic resonance imaging (MRI) to evaluate changes of posterior disc bulging and intervertebral foraminal size in the normal spine with flexion-extension movement, comparing L4-5 versus L5-S1 intervertebral levels.To determine changes in posterior disc bulging and intervertebral foraminal size with flexion-extension movement, comparing L4-5 versus L5-S1 intervertebral levels.An in vivo study of magnetic resonance kinematics with spine flexion extension.Spines of three volunteers with no history of low back pain were scanned in neutral, flexion, and extension positions in a vertically open MRI system. MRI was repeated after 6 hours of normal activity and an additional 4 hours of heavy activity with a weighted vest. Posterior bulging of the intervertebral disc and the size of intervertebral foramen were measured at the L4-5 and L5-S1 levels.With spine flexion, posterior bulging of the discs increased at L4-5 in eight of nine measurements (three different spine-loading states for each of three subjects) and L5-S1 discs in six of nine measurements. In most cases, posterior bulging decreased with extension. No significant difference was noted in the degree of disc bulge between levels. Foraminal size at L4-5 increased with flexion and decreased with extension, and the extent of these changes was greater at the L4-5 level than at L5-S1.This pilot study demonstrates two distinct behavior characteristics of the normal spine with flexion-extension movement.

  View details for PubMedID 14588361

• Temperature quantitation and mapping of frozen tissue JOURNAL OF MAGNETIC RESONANCE IMAGING Butts, K., Sinclair, J., Daniel, B. L., Wansapura, J., Pauly, J. M. 2001; 13 (1): 99-104

  Abstract

  A method was developed for quantitating the temperature within frozen tissue with the magnetic resonance (MR) parameter R2*. The pulse sequence uses half-pulse excitation and a short spiral readout to achieve echo times as short as 0.2 msec. Fiber-optic temperature sensors were inserted into bovine liver tissue. The tissue was frozen at one end while being held warm at the other end. Once steady state was reached, the parameter R2* was measured. A linear dependence of R2* on temperature was demonstrated. R2* is independent of freeze number and of the orientation of the temperature gradient with respect to the main magnetic field. Feasibility in a canine prostate during cryosurgery is demonstrated. J. Magn. Reson. Imaging 2001;13:99-104.

  View details for Web of Science ID 000171295800016

  View details for PubMedID 11169810

• The use of view angle tilting to reduce distortions in magnetic resonance imaging of cryosurgery MAGNETIC RESONANCE IMAGING Daniel, B. L., Butts, K. 2000; 18 (3): 281-286

  Abstract

  Susceptibility artifacts from magnetic resonance (MR)-compatible cryoprobes can distort MR images of iceballs. In this work, we investigate the ability of view angle tilting (VAT) to correct susceptibility induced distortions in MR images of cryosurgery. The efficacy of VAT was tested in an ex vivo bovine liver model of cryosurgery using MR-compatible cryoprobes. Artifacts on high bandwidth fast spin echo images of freezing obtained with and without VAT were compared with photographs of the actual iceball shape and size. In vivo imaging with VAT was demonstrated during percutaneous MR-guided cryosurgery of pig liver and brain. VAT was most successful in reducing probe and iceball distortions when the imaging plane was normal to the cryoprobe, and the cryoprobe was perpendicular to the main magnetic field of the scanner. VAT had the greatest benefit when used to correct MR images of freezing when the surface of the iceball was relatively near to the cryoprobe. For large iceballs, the artifact was small so the VAT correction was less important. We conclude that VAT significantly reduced distortions in the shape of the signal void corresponding to the extent of freezing visualized during MR-guided cryosurgery. This improved ability to visualize the exact location of the cryoprobe, as well as the precise shape of the iceball, particularly during initial freezing when the iceball is small, has potential to significantly improve the accuracy of MR-guided cryosurgery of small lesions, and the accuracy of MR-assisted temperature calculations that are based on precise imaging of the probe location, and boundary geometry of the iceball.

  View details for Web of Science ID 000086585100008

  View details for PubMedID 10745137

• Glenohumeral relationships during physiologic shoulder motion and stress testing: Initial experience with open MR imaging and active imaging-plane registration RADIOLOGY Beaulieu, C. F., Hodge, D. K., Bergman, A. G., Butts, K., Daniel, B. L., Napper, C. L., Darrow, R. D., Dumoulin, C. L., Herfkens, R. J. 1999; 212 (3): 699-705

  Abstract

  To test the hypotheses that open dynamic magnetic resonance (MR) imaging can (a) be used to evaluate and define normal shoulder motion in active joint motion and muscle contraction and (b) be used in conjunction with physical examination.With an open-configuration, 0.5-T MR imaging system and active image-plane tracking, 10 shoulders were studied in five asymptomatic subjects to establish normal patterns of glenohumeral motion during abduction and adduction and internal and external rotation. Preliminary studies of physical examination during MR imaging, in which a physician examiner applied mechanical force to the humeral head, were also performed.During abduction and adduction and internal and external rotation maneuvers with active subjects muscle contraction, the humeral head remained precisely centered on the glenoid fossa in all asymptomatic subjects, which is in agreement with findings of previous radiographic studies. Application of force to the humeral head by an examiner was associated with as much as 6 mm of anterior translation and 13 mm of posterior translation.Dynamic MR imaging of the glenohumeral joint is possible over a wide range of physiologic motion in vertically open systems. Use of an MR tracking coil enabled accurate tracking of the anatomy of interest. These preliminary measurements of normal glenohumeral motion patterns begin to establish normal ranges of motion and constitute a necessary first step in characterizing pathologic motion in patients with common clinical problems such as instability and impingement.

  View details for PubMedID 10478235

• Study of focused ultrasound tissue damage using MRI and histology JOURNAL OF MAGNETIC RESONANCE IMAGING Chen, L., Bouley, D., Yuh, E., D'Arceuil, H., Butts, K. 1999; 10 (2): 146-153

  Abstract

  This paper reports on an experimental study of in vivo tissue damage in the rabbit brain with focused ultrasound (FUS) using magnetic resonance imaging (MRI) and histopathological analysis. Ten ultrasonic lesions (tissue damage) were created in five rabbits using a focused ultrasound beam of 1.5 MHz, electrical power input to the transducer of 70-85 W, and an exposure duration of 15-20 seconds. T1- and T2-weighted fast spin-echo (FSE) and Fluid attenuated inversion recovery (FLAIR) sequences were used to detect the ultrasonic lesions after treatment. Imaging was performed for 4-8 hours after treatment, after which the animals were immediately sacrificed. Ultrasonic lesion diameter was measured on MRI and histological sections after correction for tissue shrinkage during the histological processing. The T1-weighted images showed lesions poorly, whereas both T2-weighted and FLAIR images showed lesions clearly. The lesion diameters on both T2 and FLAIR imaging correlated well with measurements from histology. The time delay before lesions appeared on T2-weighted imaging was 15 minutes to 1 hour, depending on the exposure location in the brain. J. Magn. Reson. Imaging 1999;10:146-153.

  View details for Web of Science ID 000084567000006

  View details for PubMedID 10441017

• Joint motion in an open MR unit using MR tracking JOURNAL OF MAGNETIC RESONANCE IMAGING Pearle, A. D., Daniel, B. L., Bergman, A. G., Beaulieu, C. F., Lang, P., Dumoulin, C. L., Darrow, R. D., Norbash, A. M., Napper, C. L., Hurtak, W., Butts, K. 1999; 10 (1): 8-14

  Abstract

  A system for active scan plane guidance during kinematic magnetic resonance (MR) examination of joint motion was developed utilizing an external tracking coil and MR tracking software. In a phantom study and during upright, weight-bearing, physiologic knee flexion, the external tracking coil maintained the scan plane through desired structures. Thus, MR tracking provides a robust method to guide the scan plane during MR imaging of active joint motion.

  View details for Web of Science ID 000081199600002

  View details for PubMedID 10398972

• 1999 Gary J. Becker Young Investigator Award. MR-guided transjugular portosystemic shunt placement in a swine model. Journal of vascular and interventional radiology Kee, S. T., Rhee, J. S., Butts, K., Daniel, B., Pauly, J., Kerr, A., O'Sullivan, G. J., Sze, D. Y., Razavi, M. K., Semba, C. P., Herfkens, R. J., Dake, M. D. 1999; 10 (5): 529-535

  Abstract

  To evaluate the performance of portal venous puncture with use of magnetic resonance (MR) guidance, and to place a transjugular intrahepatic portosystemic shunt (TIPS) in a swine model.A study of 12 swine was performed to evaluate the ability of interventional MR imaging to guide portal vein puncture and TIPS placement. Six swine had catheters placed in the right hepatic vein under C-arm fluoroscopy. A nitinol guide wire was left in the vein and the animals were then moved into an open configuration MR imaging unit. A TIPS needle set was used to puncture the portal vein using MR fluoroscopy. The animals were transferred to the C-arm, and venography confirmed portal vein puncture. A follow-up study was performed in six additional swine to place a TIPS using only MR imaging guidance. MR tracking was used to advance a catheter from the right atrium into the inferior vena cava. Puncture of the portal vein was performed and a nitinol stent was placed, bridging the hepatic parenchyma. MR venogram confirmed placement.Successful portal vein puncture was achieved in all animals. The number of punctures required decreased from 12 in the first animal to a single puncture in the last eight swine. A stent was successfully placed across the hepatic tract in all six swine.Real-time MR imaging proved to be a feasible method to guide portal vein puncture and TIPS placement in pigs.

  View details for PubMedID 10357476

• MR-guided transjugular portosystemic shunt placement in a swine model JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY Kee, S. T., Rhee, J. S., Butts, K., Daniel, B., Pauly, J., Kerr, A., O'Sullivan, G. J., Sze, D. Y., Razavi, M. K., Semba, C. P., Herfkens, R. J., Dake, M. D. 1999; 10 (5): 529-535

  Abstract

  To evaluate the performance of portal venous puncture with use of magnetic resonance (MR) guidance, and to place a transjugular intrahepatic portosystemic shunt (TIPS) in a swine model.A study of 12 swine was performed to evaluate the ability of interventional MR imaging to guide portal vein puncture and TIPS placement. Six swine had catheters placed in the right hepatic vein under C-arm fluoroscopy. A nitinol guide wire was left in the vein and the animals were then moved into an open configuration MR imaging unit. A TIPS needle set was used to puncture the portal vein using MR fluoroscopy. The animals were transferred to the C-arm, and venography confirmed portal vein puncture. A follow-up study was performed in six additional swine to place a TIPS using only MR imaging guidance. MR tracking was used to advance a catheter from the right atrium into the inferior vena cava. Puncture of the portal vein was performed and a nitinol stent was placed, bridging the hepatic parenchyma. MR venogram confirmed placement.Successful portal vein puncture was achieved in all animals. The number of punctures required decreased from 12 in the first animal to a single puncture in the last eight swine. A stent was successfully placed across the hepatic tract in all six swine.Real-time MR imaging proved to be a feasible method to guide portal vein puncture and TIPS placement in pigs.

  View details for Web of Science ID 000084345500001

• Management of biopsy needle artifacts: Techniques for RF-refocused MRI JOURNAL OF MAGNETIC RESONANCE IMAGING Butts, K., Pauly, J. M., Daniel, B. L., Kee, S., Norbash, A. M. 1999; 9 (4): 586-595

  Abstract

  Several methods were investigated to improve the depiction of biopsy needles in radiofrequency (RF)-refocused magnetic resonance imaging. Distortion correction is performed by the use of view angle tilting (VAT): a gradient is employed on the slice-select axis during readout. Needle conspicuity is increased by offsetting the gradient echo from the spin echo and by inverting the 90 degrees RF pulse slice-select gradient. VAT effectively re-registers in-plane shifts. Since this method changes the projection angle through the slice, some structures appear blurred, while other structures appear sharper. VAT does not correct errors in slice selection. Offsetting the spin echo from the gradient echo increases needle conspicuity but can result in a shift in the apparent location of the needle. Inverting the 90 degrees slice-select gradient effectively increases the needle conspicuity with no shift in the needle location. These methods provide an easy and interactive means to manipulate needle artifacts but should be used cautiously.

  View details for Web of Science ID 000080145000013

  View details for PubMedID 10232519

• Magnetic resonance imaging of frozen tissues: Temperature-dependent MR signal characteristics and relevance for MR monitoring of cryosurgery MAGNETIC RESONANCE IN MEDICINE Daniel, B. L., Butts, K., Block, W. F. 1999; 41 (3): 627-630

  Abstract

  Previously, the magnetic resonance (MR) imaging appearance of frozen tissues created during cryosurgery has been described as a signal void. In this work, very short echo times (1.2 msec) allowed MR signals from frozen tissues to be measured at temperatures down to -35 degrees C. Ex vivo bovine liver, muscle, adipose tissue, and water were imaged at steady-state temperatures from -78 degrees to +6 degrees C. Signal intensity, T2*, and T1 were measured using gradient-echo imaging. Signal intensity and T2* decrease monotonically with temperature. In the future, these MR parameters may be useful for mapping temperatures during cryosurgery.

  View details for PubMedID 10204889

• Magnetic resonance imaging of knee cartilage repair. Topics in magnetic resonance imaging Gold, G. E., Bergman, A. G., Pauly, J. M., Lang, P., Butts, R. K., Beaulieu, C. F., Hargreaves, B., Frank, L., Boutin, R. D., Macovski, A., Resnick, D. 1998; 9 (6): 377-392

  Abstract

  Cartilage injury resulting in osteoarthritis is a frequent cause of disability in young people. Osteoarthritis, based on either cartilage injury or degeneration, is a leading cause of disability in the United States. Over the last several decades, much progress has been made in understanding cartilage injury and repair. Magnetic resonance (MR) imaging, with its unique ability to noninvasively image and characterize soft tissue, has shown promise in assessment of cartilage integrity. In addition to standard MR imaging methods, MR imaging contrast mechanisms under development may reveal detailed information regarding the physiology and morphology of cartilage. MR imaging will play a crucial role in assessing the success or failure of therapies for cartilage injury and degeneration.

  View details for PubMedID 9894740

• Breast cancer: Gadolinium-enhanced MR imaging with a 0.5-T open imager and three-point Dixon technique RADIOLOGY Daniel, B. L., Butts, K., Glover, G. H., Cooper, C., Herfkens, R. J. 1998; 207 (1): 183-190

  Abstract

  To investigate the three-point Dixon technique as a method for obtaining fat-nulled images of contrast material-enhancing breast lesions with a 0.5-T open magnetic resonance (MR) imager.Real and imaginary source images were obtained with an interleaved gradient-echo sequence with a repetition time of 550 msec and echo times of 12.8, 19.8, and 26.8 msec. Twenty-four to 28 sections were obtained in the sagittal plane with a 90 degrees flip angle, 256 x 192 matrix, 3-4.5-mm section thickness, and acquisition time of 10 minutes 54 seconds. A three-point Dixon reconstruction algorithm was used to generate water-specific, fat-specific, and combined images from the raw image data. Twelve breasts in 10 patients and one healthy volunteer were imaged.Three-point Dixon images were superior to extended two-point Dixon and fat-suppressed images and to images generated by means of subtraction of three-dimensional fast spoiled gradient-echo images obtained before contrast material injection from those obtained after.Three-point Dixon imaging provides a robust method for creating fat-nulled images of enhancing breast lesions in the 0.5-T open MR environment. Water-specific three-point Dixon images are successful in regions of B0 heterogeneity and are superior to fat-suppressed images. They are much less susceptible to motion artifact than are subtraction images.

  View details for PubMedID 9530315

• Isotropic diffusion-weighted and spiral-navigated interleaved EPI for routine imaging of acute stroke MAGNETIC RESONANCE IN MEDICINE Butts, K., Pauly, J., deCrespigny, A., Moseley, M. 1997; 38 (5): 741-749

  Abstract

  An interleaved echo-planar imaging (EPI) technique is presented for the rapid acquisition of isotropic diffusion-weighted images of stroke patients. Sixteen isotropic diffusion-weighted images at three b values are acquired in less than 3 min. A spiral navigator echo is used to measure the constant and linear phase shifts across the head in both the x and y directions which result from motion during the isotropic diffusion- sensitizing gradients. The measured k-space errors are corrected during a gridding reconstruction. The gridding kernel has a constant width in kx and a variable width in ky which eliminates variable data-density ghosts. The resulting isotropic diffusion-weighted images have excellent lesion-to-normal brain contrast, very good spatial resolution, and little sensitivity to susceptibility effects in the base of the brain. Examples of diffusion-weighted images and ADC maps from several stroke patients are shown.

  View details for Web of Science ID A1997YD91100009

  View details for PubMedID 9358448

• Diffusion-weighted interleaved echo-planar imaging with a pair of orthogonal navigator echoes MAGNETIC RESONANCE IN MEDICINE Butts, K., deCrespigny, A., Pauly, J. M., Moseley, M. 1996; 35 (5): 763-770

  Abstract

  This work describes a diffusion-weighted (DW) interleaved echo-planar imaging (IEPI) method for use on either conventional whole-body scanners or scanners equipped with high-speed gradient and receiver hardware. In combination with cardiac gating and motion correction with a pair of orthogonal navigator echoes, the presented method is time-efficient, compensates for patient motions, and is less sensitive to image distortions than single-shot methods. The motion-correction scheme consists of correction for constant and linear phase terms found from the orthogonal navigator echoes. The correction for the linear phase term in the phase-encode direction includes gridding the data to the Cartesian grid. The DW IEPI was used to image a phantom rotating about the slice-select direction, and motion correction was performed to eliminate ghost artifacts arising from motion in either the readout- or phase-encoding directions. DW IEPI with motion correction was performed on a normal volunteer and on a patient with a 26-day-old region of ischemia over much of the right hemisphere.

  View details for Web of Science ID A1996UJ17500017

  View details for PubMedID 8722828

• Clinical aspects of DWI NMR IN BIOMEDICINE Moseley, M. E., Butts, K., Yenari, M. A., Marks, M., deCrespigny, A. 1995; 8 (7-8): 387-396

  Abstract

  Diffusion-weighted MR imaging (DWI) is capable of imaging ischemia-induced changes in water protons in either animal or man. Technical developments are described that allow the routine clinical utility of DWI in a stroke setting to provide objective criteria beyond the neurological exam by which the pathophysiology of stroke can be evaluated. To date, DWI has provided unique information concerning detection and evaluation of acute, symptomatic lesions from older, chronic strokes, detection and localization of small deep infarcts and reversible ischemic neurologic deficits and transient ischemia. Clinical DWI studies suggest that the temporal behaviour of ADC can critically improve the evaluation of clinical ischemia.

  View details for Web of Science ID A1995UL58700011

  View details for PubMedID 8739275

• MR-IMAGING OF THE ABDOMEN WITH A PHASED-ARRAY MULTICOIL - PROSPECTIVE CLINICAL-EVALUATION 80th RSNA Scientific Assembly Campeau, N. G., Johnson, C. D., Felmlee, J. P., Rydberg, J. N., Butts, R. K., Ehman, R. L., Riederer, S. J. RADIOLOGICAL SOC NORTH AMERICA. 1995: 769–76

  Abstract

  To prospectively compare use of a phased-array multicoil and a conventional body coil in abdominal MR imaging.Thirteen patients (seven men, six women; mean age, 55 years) underwent imaging with a phased-array multicoil and with a conventional body coil. Four pulse sequences were used: T2-weighted spin echo (SE), magnetization-prepared gradient-recalled echo (GRE), breath-hold fast SE, and echo planar (EP).Lesion detection improved the most on fast SE, multicoil-acquired images. Signal-to-noise ratio (S/N) increased 64% with fast SE (P = .0005) and EP (P < .0109) sequences. Contrast-to-noise ratio (C/N) doubled (P < .05) with T2-weighted SE sequences. Lesion conspicuity improved on multicoil-acquired images with all fast sequences (magnetization-prepared GRE, P = .015; fast SE, P = .002; EP imaging, P = .013). There was little difference in respiratory and vascular artifact. Depiction of most abdominal structures improved (P < .01).Use of the phased-array multicoil provides better MR images of the abdomen than does use of a conventional body coil.

  View details for Web of Science ID A1995QZ80200035

  View details for PubMedID 7754009

• DUAL-ECHO INTERLEAVED ECHO-PLANAR IMAGING OF THE BRAIN MAGNETIC RESONANCE IN MEDICINE Slavin, G. S., Butts, K., Rydberg, J. N., Jack, C. R., Riederer, S. J. 1995; 33 (2): 264-270

  Abstract

  An interleaved echo-planar imaging (EPI) technique is described that provides images from 20 sections of the brain at two echo times (27 and 84 ms) in 1:05. Six echoes per image per repetition are collected in 24 repetitions of the pulse sequence. MR images of the brain obtained from five volunteers using the dual-echo EPI sequence, fast spin-echo (FSE), and conventional dual-echo spin-echo were evaluated qualitatively for diagnostic use and quantitatively for relative signal-to-noise ratio (SNR), contrast, and contrast-to-noise ratios (CNR).

  View details for Web of Science ID A1995QE69200017

  View details for PubMedID 7707919

• THE EFFECT OF RESPIRATION ON THE CONTRAST AND SHARPNESS OF LIVER-LESIONS IN MRI MAGNETIC RESONANCE IN MEDICINE Butts, K., Riederer, S. J., Ehman, R. L. 1995; 33 (1): 1-7

  Abstract

  This work demonstrates the effects of through-plane motion due to respiration on contrast and sharpness of liver lesions in MRI. The effects of slice coverage with and without such respiratory motion is also reported. This work is comprised of two parts: a theoretical prediction of liver-lesion contrast and blur with and without respiration and an experimental validation using gel phantoms of the predicted results. Both theory and experiment show a loss of contrast, increasing with amplitude of the peak-to-peak motion. The loss of contrast for a 5-mm lesion at normal respiration of 15 mm peak-to-peak superior-inferior motion is approximately 10% with a low order sorted respiratory ordered phase encoding acquisition and approximately 50% for an unsorted acquisition. Lesion blur is greatest for the low order sorted acquisition while the unsorted and high sort acquisitions maintain edge definition. Breath-hold imaging is potentially superior to nonbreath-hold imaging in liver lesion contrast and edge definition, but is more sensitive to inadequate slice coverage.

  View details for Web of Science ID A1995PZ80800001

  View details for PubMedID 7891521

• IMAGING OF CEREBRAL ACTIVATION AT 1.5-T - OPTIMIZING A TECHNIQUE FOR CONVENTIONAL HARDWARE RADIOLOGY Thompson, R. M., Jack, C. R., Butts, K., Hanson, D. P., Riederer, S. J., Ehman, R. L., HYNES, R. W., Hangiandreou, N. J. 1994; 190 (3): 873-877

  Abstract

  To empirically optimize a two-dimensional magnetic resonance (MR) imaging technique for detecting changes in signal intensity during cerebral activation with a standard clinical imager.Visual activation experiments were performed while imaging parameters were manipulated in a serial fashion, to test their effect on the percentage change in signal intensity (PCSI). The parameters tested were section thickness, echo time (TE), field of view (FOV), flip angle, radio-frequency (RF) spoiling, number of readout points, and number of signals averaged.The PCSI for visual activation experiments was typically in the 1%-5% range. The best results were achieved with a small section thickness, long TE, and large FOV. Variations in other acquisition parameters had a negligible influence on the PCSI.Good results can be obtained at functional MR imaging with standard 1.5-T hardware. Markedly improved results can be obtained by optimizing several key variables, namely, section thickness, TE, and FOV.

  View details for Web of Science ID A1994MX69800049

  View details for PubMedID 8115643

• INTERLEAVED ECHO-PLANAR IMAGING ON A STANDARD MRI SYSTEM MAGNETIC RESONANCE IN MEDICINE Butts, K., Riederer, S. J., Ehman, R. L., Thompson, R. M., Jack, C. R. 1994; 31 (1): 67-72

  Abstract

  This work describes an interleaved echo planar imaging (EPI) method for use on a standard whole body scanner. The data acquisition is divided into two to eight repetitions rather than one to two, as implemented by dedicated EPI systems. Interleaving allows the use of a lower sampling bandwidth with a significant increase in signal-to-noise. The method also has the advantages of relative ease of implementation, no need for postprocessing to remove image distortion, and no need for shimming on a case-by-case basis. The interleaved EPI method was applied to two applications ideally suited to EPI: breathhold T2-weighted abdominal imaging and functional imaging. In vivo liver-lesion contrast as measured in a 35-patient study showed increased contrast for the interleaved EPI by an average factor of 1.21 (+/- 0.34) over conventional spin-echo imaging. CNR measurements showed the EPI to be comparable with conventional spin echo with a relative factor of 1.00 (+/- 0.36). Functional imaging with an eight-shot interleaved EPI sequence provided 128 x 128 images of cerebral activation during bilateral finger tapping.

  View details for Web of Science ID A1994MP54200010

  View details for PubMedID 8121272

• SENSORY-MOTOR CORTEX - CORRELATION OF PRESURGICAL MAPPING WITH FUNCTIONAL MR-IMAGING AND INVASIVE CORTICAL MAPPING RADIOLOGY Jack, C. R., Thompson, R. M., Butts, R. K., Sharbrough, F. W., Kelly, P. J., Hanson, D. P., Riederer, S. J., Ehman, R. L., Hangiandreou, N. J., Cascino, G. D. 1994; 190 (1): 85-92

  Abstract

  To describe a clinically useful application of functional magnetic resonance (MR) imaging--presurgical mapping of the sensory motor cortex--and to validate the results with established physiologic techniques.Functional MR mapping of the sensory motor cortex was performed in two women, aged 24 and 38 years. Both had intractable, simple partial motor seizures due to tumors located in or near the sensory motor cortex. They subsequently underwent invasive cortical mapping--direct cortical stimulation and/or sensory-evoked-potential recording--to localize the affected sensory motor area prior to tumor resection.In both patients, the functional MR study demonstrated task activation of the sensory motor cortex. In both cases, results of cortical functional mapping with invasive techniques matched those obtained with functional MR imaging.Presurgical mapping of the sensory motor cortex is a potentially useful clinical application of functional MR imaging.

  View details for Web of Science ID A1994MW25300019

  View details for PubMedID 8259434

• ECHO-PLANAR IMAGING OF THE LIVER WITH A STANDARD MR-IMAGING SYSTEM RADIOLOGY Butts, K., Riederer, S. J., Ehman, R. L., Felmlee, J. P., Grimm, R. C. 1993; 189 (1): 259-264

  Abstract

  A multisection, whole-body echo-planar imaging (EPI) sequence was developed to obtain T2-weighted images of the liver in one 18-second breath hold with a standard magnetic resonance (MR) imaging system.This capability was achieved by dividing the data acquisition period into eight interleaved segments rather than one or two as implemented previously with EPI systems having high-power gradient subsystems.The interleaved echo-planar images had excellent depiction of anatomy and no identifiable respiratory artifact. In 26 lesions in 12 patients, the eight-shot echo-planar images (2,000/66 [repetition time msec/echo time msec]) had superior contrast compared with conventional T2-weighted spin-echo (SE) images (2,500/60) by an average factor of 1.22 +/- 0.31 (standard deviation) and an average contrast-to-noise ratio relative to conventional T2-weighted SE images of 0.85 +/- 0.22.With a conventional MR imaging system, breath-hold T2-weighted echo-planar images of the liver are comparable in diagnostic quality to conventional T2-weighted SE images.

  View details for Web of Science ID A1993LY02300051

  View details for PubMedID 8396785

• PHASE-VELOCITY MAPPING WITH A REAL-TIME LINE SCAN TECHNIQUE MAGNETIC RESONANCE IN MEDICINE Butts, K., Hangiandreou, N. J., Riederer, S. J. 1993; 29 (1): 134-138

  Abstract

  A real-time, 20-Hz, one-dimensional MR velocity imaging technique is described. A two-dimensional RF pulse excites a 3-cm diameter column. Velocity maps are formed from the phase difference between successive flow encoded and compensated acquisitions. A three-point subtraction variation provides reduced sensitivity to static spins.

  View details for Web of Science ID A1993KJ34900023

  View details for PubMedID 8419735

• ANALYSIS OF FLOW EFFECTS IN ECHO-PLANAR IMAGING JOURNAL OF MAGNETIC RESONANCE IMAGING Butts, K., Riederer, S. J. 1992; 2 (3): 285-293

  Abstract

  The effects on the phase of spins moving during echo-planar imaging (EPI) acquisition were studied. Standard single-shot and interleaved multishot blipped EPI acquisitions were considered, assuming either high gradient strength and slew rates or standard gradient strength and slew rates. A spiral k-space trajectory was also considered. Flow components in the section-select and phase- and frequency-encoding directions were analyzed separately. While the effect of flow in the section-select direction is identical to that in a standard two-dimensional Fourier transform (2DFT) acquisition, flow in the phase- or frequency-encoding directions can have substantial effects on the image, different from that in 2DFT imaging. The magnitude of these effects, which include displacement, distortion, and/or ghosting of vascular structures, is analyzed and predicted for a given velocity and direction of flow, the specific acquisition sequence, and the strength and slew rate of the gradients. For example, 50-cm/sec flow along the phase-encoding direction can cause a blurring of 1.25 cm full width at half maximum for blipped EPI with high-strength gradients, assuming a 40-cm field of view and 64 x 64 matrix.

  View details for Web of Science ID A1992HV08100005

  View details for PubMedID 1627863

• T2-WEIGHTED SPIN-ECHO PULSE SEQUENCE WITH VARIABLE REPETITION AND ECHO TIMES FOR REDUCTION OF MR IMAGE ACQUISITION TIME RADIOLOGY Butts, R. K., Farzaneh, F., Riederer, S. J., Rydberg, J. N., Grimm, R. C. 1991; 180 (2): 551-556

  Abstract

  Use of intraacquisition modification of pulse-sequence parameters to reduce acquisition time for conventional T2-weighted spin-echo images was evaluated. With this technique (variable-rate spin-echo pulse sequence), the repetition time and echo time (TR msec/TE msec) were reduced during imaging as a function of the phase-encoding view. To maintain T2-based contrast, TR and TE for the low-spatial-frequency views were left at their prescribed values (eg, 2,000/80). TR and TE for the high-spatial-frequency views were progressively reduced during imaging (eg, to 1,000/20). Acquisition time was reduced by as much as 25%. In one pulse sequence, the duration of multisection imaging nominally performed at TR 2,000 and with 256 phase-encoding views was reduced from 9 minutes 30 seconds to 6 minutes 30 seconds. In all sequences, edges and small structures were enhanced, and T2 contrast was somewhat decreased in high spatial frequencies. Filtering of the raw data before reconstruction can suppress these effects and provide a net increase in contrast-to-noise ratio.

  View details for Web of Science ID A1991FW93300051

  View details for PubMedID 2068326